Protegrins and their derivatives are a new class of peptide antibiotics based on mammalian antimicrobial peptides. Their pharmacological properties include an unusually broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi and some enveloped viruses. Preclinical and clinical studies of the lead compound, IB-367, developed for topical applications, show promise for the prevention of chemotherapy- and radiation-induced oral mucositis.