Significance Novel antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections. Venoms constitute a treasure trove of novel potential medicines. Here, we converted a peptide derived from venom into potent antimicrobials capable of resolving otherwise lethal infections in mice. We demonstrate that the peptide acts directly on bacteria by targeting their membrane, while also modulating the host immune response and dampening unwanted inflammation. Venom-derived molecules such as the ones described here represent an exciting new source of antibiotics.