All the articles included in this mini review (Table 1) focused on species belonging to the order Hymenoptera, confirming this group as the principal source of insect venoms investigated for antimicrobial potential. A total of 15 peer-reviewed studies from five countries examined venoms from 13 insect species, comprising one ant (Menk et al., 2023), five bees (Čujová et al., 2013; Kim et al., 2013; Ko et al., 2017; Ko et al., 2020; Park et al., 2018; Jeon et al., 2024), and seven wasps (das Neves et al., 2016; Ha et al., 2017; Rangel et al., 2017; Ganavi and Ramesh, 2024; Konno et al., 2019; Silva et al., 2017; Silva et al., 2020).

South Korea accounted for the largest share of publications (six), followed by Brazil (five), Czech Republic (two) and other countries with one article: India, and Japan. Most investigations were conducted within universities (14 out of 15 studies), while only one originated from a research institute (Rangel et al., 2017). Among these, four studies employed animal models to assess in vivo antimicrobial activity (das Neves et al., 2016; Silva et al., 2017; Silva et al., 2020; Jeon et al., 2024), and none reported clinical trials in humans.

The antimicrobial peptide (AMP) repertoire of insect venoms is taxonomically diverse, with most known examples described from Hymenoptera, including wasps, bees, and ants. Venoms from solitary and social wasps contain families such as mastoparans, anoplin, and polydim-I, which exhibit strong antimicrobial activities (Cabrera et al., 2019; Ganavi and Ramesh, 2024; das Neves et al., 2016; Silva et al., 2017; Silva et al., 2020). Ant venoms contribute ponericins, a heterogeneous group divided into subfamilies (G, W, and L) with distinct antibacterial spectra (Orivel et al., 2001; Menk et al., 2023). In bees, notable examples include osmin from Osmia rufa, melectin from Melecta albifrons, and macropin from Macropis fulvipes, all of which exhibit potent antibacterial activity, with melectin and macropin additionally showing low cytotoxicity toward mammalian cells (Jeon et al., 2024; Ko et al., 2017; Ko et al., 2020). A list of references of studies of Hymenoptera venom molecules with antibiotic potential can be found below (Table 1).

Non-Hymenopteran AMPs are less documented, but Hemipteran reduviid bugs (Rhynocoris marginatus, Catamirus brevipennis) produce venom with antibacterial activity against several human pathogens (Sahayaraj et al., 2006), however, this article was not included in Table 1 because it was published more than 15 years ago. Computational mining and transcriptomic studies have predicted additional cecropin-like and defensin-like peptides across other insect taxa, underscoring a largely untapped diversity (Guan et al., 2025; Menk et al., 2023).

Venom AMPs often serve a dual function: disabling prey and preventing microbial contamination. In predatory ants such as Pachycondyla goeldii, ponericins likely reduce pathogen load from prey carcasses introduced into the nest (Orivel et al., 2001). Social wasps, frequently exposed to environmental microbes, may use venom AMPs such as polydim-I and mastoparans for colony-level pathogen defense (das Neves et al., 2016; Ganavi and Ramesh, 2024). For reduviid bugs, antimicrobial venom factors may protect the predator from opportunistic infections acquired during feeding on immunocompromised prey (Sahayaraj et al., 2006; Yan and Adams, 1998).

Evolutionary pressures from both prey–predator interactions and communal living could have selected for peptides with potent and broad antimicrobial activity (Ascoët et al., 2023; Cabrera et al., 2019).

Most venom-derived AMPs are short (10–35 amino acids), linear, cationic, and amphipathic, often adopting an α-helical structure in membrane-mimicking environments (Cabrera et al., 2019; Konno et al., 2019; Ko et al., 2020). These structural features enable insertion into and disruption of bacterial membranes. Net positive charge facilitates electrostatic attraction to negatively charged microbial surfaces, while hydrophobic faces promote membrane penetration. Variations in hydrophobicity and helix stability correlate with differences in antimicrobial potency and cell selectivity (Ko et al., 2017; Ko et al., 2020). Some peptides, such as polydim-I, also show stability in the presence of physiological salt concentrations, a desirable pharmacological trait (das Neves et al., 2016; Rangel et al., 2017).

Venom AMPs primarily target bacterial membranes through mechanisms such as pore formation, membrane thinning, and detergent-like disruption (Cabrera et al., 2019; Konno et al., 2019; Ko et al., 2017). Electrostatic binding to lipopolysaccharide (LPS) in Gram-negative bacteria or peptidoglycan in Gram-positive bacteria initiates the interaction (Ko et al., 2020; Oñate-Garzón et al., 2016). Certain peptides, including macropin, not only disrupt cell membranes but also inhibit biofilm formation and eradicate established biofilms of drug-resistant pathogens (Ko et al., 2017). Synergy with conventional antibiotics has been documented, enhancing bacterial clearance at lower doses (Ko et al., 2020). Differences in lipid composition between Gram-positive and Gram-negative membranes influence peptide susceptibility, explaining variable spectra within a single AMP family (Orivel et al., 2001; Menk et al., 2023).

AMPs from insect venoms display a broad range of activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains such as Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli (Ko et al., 2017; Ko et al., 2020). Some, like polydim-I, show potent antimycobacterial activity in vitro and in vivo against Mycobacterium abscessus (das Neves et al., 2016; Rangel et al., 2017). Although less common, certain venom peptides also exhibit antifungal (Oñate-Garzón et al., 2016; Čujová et al., 2013; Kim et al., 2013) and antiparasitic activity (Konno et al., 2019). Spectrum differences can be significant even within a peptide family—for example, ponericin subfamilies differ in Gram-type specificity and potency (Orivel et al., 2001).

In vivo studies demonstrate that insect venom AMPs can effectively reduce bacterial burdens without significant host toxicity. Polydim-I significantly reduced lung, spleen and liver bacterial loads in mice infected with M. abscessus by provoking cell wall disruption without exhibiting cytotoxicity toward mammalian cells (das Neves et al., 2016). Effectiveness in vivo of another mastoparan peptide, Polybia-MPII, was reported by Silva et al. (2017) in topical treatment of skin infections of S. aureus in mice, reducing bacterial load and promoting wound healing. Additionally, the synthetic peptide mast-MO was tested in skin and intraperitoneal infections in mice with enhanced antimicrobial activity by destabilizing the bacterial outer membrane and exhibited immunomodulatory properties by increasing leukocyte migration to the infection site and repressing proinflammatory factors (Silva et al., 2020). Although the mastoparan family was discovered decades ago, it has been poorly evaluated using in vivo tests (Silva et al., 2017).

Hemolysis assays generally reveal low to moderate activity, with some peptides, like melectin and macropin, showing strong selectivity for bacterial over mammalian cells (Ko et al., 2017; Ko et al., 2020). Nonetheless, peptides such as certain mastoparans exhibit dose-dependent hemolysis, highlighting the importance of balancing efficacy and cytotoxicity (Cabrera et al., 2019; Silva et al., 2017).

Results of the peptide osmin are also interesting by significantly reducing K. pneumoniae bacterial burden and pro-inflammatory cytokine expressions in infected mouse model (Jeon et al., 2024).

Advances in peptide synthesis and recombinant expression have facilitated the production of native and analog insect venom AMPs. Solid-phase peptide synthesis (SPPS) has been used to create both wild-type sequences and modified variants with improved activity profiles (Cabrera et al., 2019; Silva et al., 2020). Recombinant systems, including E. coli secretion pathways, enable cost-effective production of peptides like mastoparan V1 (Ha et al., 2017). Optimized analogs have demonstrated improved antimicrobial potency against MDR bacteria and, in some cases, reduced hemolysis (Silva et al., 2020; Rangel et al., 2017).

Research has so far identified a limited but diverse set of insect venom AMPs, including mastoparans from social wasps (Silva et al., 2017; das Neves et al., 2016; Ha et al., 2017; Konno et al., 2019; Cabrera et al., 2019; Rangel et al., 2017), melectin (Ko et al., 2020), macropin (Monincová et al., 2014) and panurgines (Čujová et al., 2013) from solitary bees, and Kazal-type inhibitors (Kim et al., 2013) from honeybees. Venomic and transcriptomic approaches have expanded the scope, identifying putative peptide arsenals in ants such as Odontomachus chelifer (Menk et al., 2023) and Tetramorium bicarinatum (Ascoët et al., 2023). Despite this progress, insect venom AMPs remain underexplored compared to other venomous taxa, and the true chemical diversity is likely far greater. Future bioprospecting efforts should emphasize deep sequencing and integrative venomics in unexplored insect lineages, coupled with functional screening.

Only a few venom peptides have progressed to in vivo validation. Notably, mastoparan-derived peptides and engineered variants demonstrated efficacy in murine models of lethal bacterial infection (Silva et al., 2020). Polydim-I was also effective against mycobacteria infections and multi-resistant strains, it also showed to be safe to mice on in vivo assays and against mammal cells in vitro (das Neves et al., 2016; Rangel et al., 2017). These successes represent critical translational milestones. However, most other insect venom peptides remain at the in vitro stage, with limited pharmacokinetic, stability, or immunogenicity assessments. Systematic pre-clinical pipelines, including toxicity profiling and formulation strategies, are urgently needed to move the field closer to clinical trials.

Venom peptides are inherently unstable in physiological environments, where proteolysis rapidly degrades them. To date, a few studies have addressed delivery challenges beyond demonstrating activity in buffered systems. Some analogues, such as mastoparan derivatives, have been modified for improved stability and immunomodulation (Silva et al., 2020), but further exploration of delivery systems—nanoparticles, liposomes, and peptidomimetics—remains essential for clinical translation.

While most studies focus on bactericidal properties, several insect venom AMPs also display antifungal (das Neves et al., 2016), antibiofilm (Rangel et al., 2017), or immunomodulatory effects (Silva et al., 2020). This multifunctionality may allow development of dual-action therapeutics that both kill pathogens and enhance host responses. Moreover, selective immunomodulation, as demonstrated by Silva et al. (2020), could mitigate harmful inflammation in infections. Future studies should explore this broader therapeutic landscape, as it could differentiate insect venom peptides from other AMP sources.

Despite the promise of those 15 studies, several gaps persist: