Antimicrobial resistance (AMR) remains one of the most serious and urgent global health challenges, which significantly limits the effectiveness of conventional antibiotics and antifungal agents. In this context, antimicrobial peptides (AMPs) represent a promising class of next-generation therapeutics due to their broad-spectrum activity, rapid killing kinetics, diverse mechanisms of action, and comparatively low propensity for resistance development. Despite substantial progress in recent years, major gaps persist in AMP discovery, optimization, mechanistic understanding, and translational applications. Addressing these challenges requires efforts to develop novel and effective AMPs, elucidate their modes of action, minimize host toxicity, and enhance stability, selectivity, and therapeutic applicability.

This Research Topic welcomes cutting-edge contributions that advance the understanding and application of AMPs across human healthcare, agriculture, food preservation, and environmental settings. Studies addressing the discovery, rational design, functional characterization and systemic in vivo efficacy of AMPs targeting bacterial and fungal pathogens are particularly encouraged.

We welcome submissions including, but not limited to, the following themes:

• Discovery and rational design of novel AMPs using machine learning, metagenomics, proteogenomics, high-throughput screening, and computational approaches for activity prediction and peptide optimization
• Structure–function relationships and molecular mechanisms underlying AMP activity
• Microbial resistance or tolerance mechanisms against antimicrobial peptides
• In vitro and in vivo evaluations of AMP efficacy, including membrane interactions, biofilm inhibition, fungal cell wall targeting, and systemic efficacy in translatable infection models
• Combination therapies involving AMPs and existing antimicrobial agents to enhance efficacy and mitigate resistance
• Peptide modification strategies to improve stability, selectivity, toxicity, pharmacokinetics, and pharmacodynamics
• Production strategies, delivery systems, and translational challenges associated with AMP-based therapeutics

Computational studies are encouraged when supported by experimental or functional validation, or when they provide rigorous benchmarking against experimentally validated datasets. Submissions should prioritize clear biological and mechanistic insight, robust validation, or demonstrable translational relevance. Studies that are purely descriptive or limited to screening-level analyses will not be considered. Methodological contributions must address applicability, limitations, and value to experimental AMP research.

A broad range of article types is encouraged, including Hypothesis & Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Systematic Review, Technology and Code, with the overarching goal of advancing antimicrobial peptides as versatile and powerful tools to combat microbial pathogens in an era of escalating antimicrobial resistance.

Are you interested in contributing a manuscript to this Research Topic?

Advances in the Discovery and Characterization of Novel Antimicrobial Peptides for Combating Drug-Resistant Microbial Pathogens