Wound infections are a growing public health issue, worsened by drug-resistant strains. Quercetin (Que) has shown anti-inflammatory, antioxidant, and antimicrobial properties, but its limited bioavailability hinders therapeutic use. This study introduces a multifunctional self-assembly nanoplatform, QHCNPs, encapsulating quercetin with hordein/chitosan to enhance stability and bioavailability. Transmission electron microscopy and particle size analysis revealed that QHCNPs are spherical structures with a diameter of 435.5 ± 2.9 nm and a Zeta potential of +11.0 mV. QHCNPs demonstrated excellent stability, low cytotoxicity, and MIC values of 512 ppm against Staphylococcus aureus (S. aureus) and 256 ppm against methicillin-resistant Staphylococcus aureus (MRSA). In a bacterial wound model, QHCNPs outperformed quercetin alone by accelerating wound healing, eliminating bacteria, reducing inflammatory markers, scavenging reactive oxygen species (ROS), and promoting collagen and blood vessel regeneration. These results establish QHCNPs as a promising non-antibiotic therapy for treating drug-resistant wound infections, supporting further exploration for clinical applications.