Artificial dressings composed of degradable polymer materials have a wide range of applications in skin repair. The structure and properties, in particular, the antibacterial properties, of the material surface are crucial for biological processes such as cell adhesion, proliferation, and skin regeneration. In this study, we aimed to prepare poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds modified by polydopamine using electrospinning technology in order to produce polydopamine-modified degradable PLGA nanocomposites. The polydopamine-PLGA scaffold was endowed with excellent protein adhesion ability through the cross-linking of two biologically active factors, basic fibroblast growth factor (bFGF) and ponericin G1, significantly improving skin repair ability. The electrospun nanofiber scaffold was shown to have a structure similar to that of the natural cell matrix and created a more favorable microenvironment for cell growth. Surface modification by polydopamine dramatically improved the hydrophilicity of the nanofiber scaffold, increasing its ability to absorb active factors and its biocompatibility. The bFGF and ponericin G1 loaded onto the scaffold surface (PDA-PLGA/bFGF/ponericin G1 nanofiber scaffold) strongly promoted the antibacterial and cell proliferation-promoting properties and greatly enhanced the adhesion and proliferation of cells on the scaffold surface. The nanofiber scaffold also promoted wound healing and tissue collagen production in a rat wound healing model. Together, these findings indicate that the polydopamine-PLGA/bFGF/ponericin G1 nanofiber scaffold exhibits good biocompatibility and antibacterial properties, suggesting that it possesses potential value for skin tissue regeneration applications.