Aims　To　address　the　increasingly　serious　challenge　of　the　transmission　of　foodbrone　pathogens　in　the　food　chain.　Methods　and　results　In　this　study,　we　employed　rational　design　strategies,　including　truncation,　amino　acid　substitution,　and　heterozygosity,　to　generate　seven　engineered　peptides　with　α-helical　structure,　cationic　property,　and　amphipathic　characteristics　based　on　the　original　Abhisin　template.　Among　them,　as　the　hybird　antimicrobial　peptide　(AMP),　AM　exhibits　exceptional　stability,　minimal　toxicity,　as　well　as　broad-spectrum　and　potent　antimicrobial　activity　against　foodborne　pathogens.　Besides,　it　was　observed　that　the　electrostatic　incorporation　demonstrates　by　AM　results　in　its　primary　targeting　and　disruption　of　the　cell　wall　and　membrane　of　Escherichia　coli　O157:　H7　(EHEC)　and　methicillin-resistant　Staphylococcus　aureus　(MRSA),　resulting　in　membrane　perforation　and　enhanced　permeability.　Additionally,　AM　effectively　counteracts　the　deleterious　effects　of　lipopolysaccharide,　eradicating　biofilms　and　ultimately　inducing　the　demise　of　both　food　spoilage　and　pathogenic　microorganisms.　Conclusions　The　findings　highlight　the　significant　potential　of　AM　as　a　highly　promising　candidate　for　a　novel　food　preservative　and　its　great　importance　in　the　design　and　optimization　of　AMP-related　agents.　Impact　Statement　The　present　manuscript　represents　the　first　study　on　the　application　of　the　original　Abhisin　template　for　generating　engineered　antimicrobial　peptides　(AMPs)　with　potent　activity　and　high　biocompatibility　through　rational　design　strategies,　thereby　providing　a　valuable　reference　for　designing　novel　AMPs　to　combat　foodborne　pathogens.　©　2024　Oxford　University　Press.　All　rights　reserved.