Intractable skin defects, which involve excessive inflammation and bacterial infections, caused by burns, trauma, and diabetes are a major challenge for clinicians. Compared with traditional skin transplantation, tissue-engineered skin has the advantages of a wide range of sources, prominent biological activity, and no damage to the donor area during the operation. Therefore, an effective wound-healing mat with antibacterial, anti-inflammatory, and microvascularization bioactivities is urgent to be developed. In this study, we have synthesized a poly(ester-urethane)urea/silk fibroin/magnolol nanofibrous composite mat (PSM) through electrospinning and post-hydrogen bond cross-linking. The results show that the hybrid magnolol has no adverse effect on the microstructure, porosity, wettability, and mechanical properties of PSM. Antibacterial experiments and cytocompatibility in vitro have proved that the addition of magnolol significantly improves the antibacterial ability and promotes cell adhesion and proliferation of PSM. In addition, the wound model of rat back and H&E staining, Masson trichrome staining, and CD31 and CD68 immunofluorescence staining were performed for evaluating the therapeutic efficiency of PSM. All the results show that the better wound treatment effect of magnolol hybrid nanofibrous mats in infectious skin tissue defected repair indicates their great potential for wound healing clinically.