The emergence of drug-resistant microorganisms has threatened global health, and microbial infections have severely limited the use of medical materials. For example, the attachment and colonization of pathogenic bacteria to medical implant materials can lead to wound infections, inflammation and complications, as well as implant failure, shortening their lifespan and even resulting in patient death. In the era of antibiotic resistance, antimicrobial drug discovery needs to prioritize unconventional therapies that act on new targets or adopt new mechanisms. In this regard, supramolecular antimicrobial peptides have emerged as attractive therapeutic platforms, both as bactericides for combination antibiotics and as delivery vehicles. By taking advantage of their programmable intermolecular and intramolecular interactions, peptides can be modified to form higher-order structures (including nanofibers and nanoparticles) with unique functionality. This paper begins with an analysis of the relationship between peptide self-assembly and antimicrobial activity, describes in detail the research and development of various self-assembled antimicrobial peptides in recent years, and finally explores different combinatorial strategies for self-assembling antimicrobial peptides.