Infectious wounds with exaggerated reactive oxygen species in surrounding tissues can significantly impede high-quality skin tissue repair, which necessitates alternative wound management strategies. Hyperbranched poly-l-lysine (HBPL) is a broad-spectrum cationic antimicrobial polypeptide with potent bactericidal activity and good biocompatibility, making it a promising alternative to conventional antibiotics. Similarly, chlorogenic acid (CGA) is a natural plant-derived polyphenol, which possesses strong free radical scavenging ability and anti-inflammatory potential. Herein, we have explored the synergistic effect of HBPL and CGA to promote anti-infective wound healing in electrospun poly(l-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF) fibers. The HBPL was directly loaded into the fibers while CGA was first chelated onto the surface of hollow mesoporous silica microspheres via metal coordination and these microspheres were loaded into fibers for sustained release. The composite scaffold exhibited significant anti-inflammatory activity by modulating macrophages polarization towards anti-inflammatory phenotype. Besides, scaffolds exhibited distinct antibacterial efficacy against Staphylococcus aureus and Escherichia coli in vitro. Moreover, in vivo evaluation of these dressings in a Staphylococcus aureus infected full-thickness excisional defect model significantly promoted epithelial reconstruction, resolved inflammation, scavenged reactive oxygen clearance, and enhanced the deposition of collagen 2 weeks post-operatively, and outperformed all control groups. This multidimensional synergistic wound healing strategy presents a promising therapeutic platform for the effective management of infected wounds.