Bacterial infections exacerbate the formation of bacterial biofilms, leading to resistance to traditional drugs, persistent infection, and even threatening patient’s life. Efficient antimicrobial materials against drug-resistant bacterial biofilms are highly desired. In this study, a photodynamic nanodrug with bacterial targeting was constructed by cooperative coordination of zinc ion with an antimicrobial peptide with hydrophobic tripeptides on the side chains and the photosensitizer chlorin e6. The supramolecular nanodrug with a uniform spherical structure possessed high photosensitizer loading capacity and enhanced photodynamic efficacy, which could deep penetrate and eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms upon 655 nm laser irradiation. Furthermore, in vivo experiments verified the efficient elimination of MRSA biofilms on implanted catheters. This study provides a novel strategy to fabricate metalloprotein-inspired supramolecular photodynamic nanodrugs against drug-resistant bacterial biofilms-associated infections in vivo.