The invention described herein relates to compositions of novel antimicrobial peptides that comprise hydrophobic and cationic residues, based on monomeric tri-peptide units. The peptides of the present invention exhibit high antibacterial activity and low hemolytic activity. The invention further provides compositions comprising these antimicrobial peptides and methods of use thereof for killing, reducing the growth of, or preventing the growth of microorganisms. The invention also provides antimicrobial substrates, medical devices, protective garments and barrier materials comprising the peptides of the present invention.