UNLABELLED: The escalating threat of antibiotic-resistant bacteria has heightened global interest in antimicrobial peptides as promising candidates due to their potent broad-spectrum activity and low likelihood of resistance development. Despite this potential, these peptides face challenges, including modest bactericidal efficacy, insufficient safety assessment, and expensive production. In this study, we systematically evaluated a panel of nine AMP variants of PGLa, a natural AMP derived from IMPORTANCE: AMPs are innate defense molecules in animals, plants, and microorganisms. Notably, one-third of these peptides in databases originate from amphibians. We discovered that naturally weak AMPs from this source can be enhanced through artificial design. Specifically, variant DiPGLa-H showed superior germicidal efficacy and cell selectivity both