Overuse and misuse of antibiotics has led to increasing bacterial resistance. We have synthesized mutant forms of gramicidin A (gA), a fifteen residue amino-acid peptide originally from Bacilllus brevis, to eliminate bacteria through a new mechanism. Like other antimicrobial peptides, these gA mutants can destroy bacterial pathogens by disrupting their cellular membrane, a unique anti-bacteria mechanism that is difficult for bacteria to acquire resistance. Compared to original gA which has been used as active ingredient in some antibiotic ointment, these gA mutants are highly potent against bacteria but more water-soluble, less-toxic to mammalian cells. These advantages position them as promising systemic antibiotics.