Chronic wound infection is a leading cause of mortality in injured patients worldwide. At present, available systemic antibiotic treatments have an insufficient tissue penetration ability and allow the development of antibiotic-resistant pathogens. The identification of therapeutic agents with wound healing and antimicrobial functions is necessary to heal the wound and cure infections. Our report shows that the antimicrobial peptide (AMP) Epinecidin-1 (Epi-1) efficiently heals MRSA-infected heat burn injuries and provides protection from infection in mouse and pig model. Our results demonstrate that the biomaterial Epi-1 heals wounds through increasing epithelial cell proliferation, vascularization, and the formation of collagen and controls MRSA infection-mediated sepsis in pigs.