The increasing prevalence of multidrug-resistant bacteria is a significant global health threat. In contrast to conventional antibiotic treatments, photodynamic therapy (PDT) offers a promising alternative by reducing the bacterial adaptability to antibiotics and bactericides. However, traditional photosensitizers encounter poor antimicrobial efficacy due to poor hydrophilicity of photosensitizers, short lifespan, narrow diffusion radius of reactive oxygen species (ROS), and the risk of exacerbating inflammation. In this study, we report a bacterial-targeting supramolecular nanophotosensitizer for combating multidrug resistant bacteria. The nanophotosensitizer, formed through host–guest interactions and self-assembly of tetra-cyclodextrin-modified silver porphyrin (AgTPP-CD4), adamantyl-modified phenylboronic acid (Ad-PBA), and curcumin (Cur), can effectively target and kill methicillin-resistant Staphylococcus aureus (MRSA). Moreover, it reduces inflammation and promotes wound healing in MRSA-infected wounds without inducing drug resistance. The combination of supramolecular chemistry and targeted PDT offers a promising strategy for combating multidrug-resistant bacterial infections.