Polylactide−polyglycolide (PLGA) is one of the most attractive polymeric biomaterials used to fabricate medical devices for drug delivery and tissue engineering applications. Nevertheless, the utilization of PLGA in load-bearing applications is restricted due to its inadequate mechanical properties. This study examines the potential of recombinant silk fibroin (eADF4), a readily producible biomaterial, as a reinforcing agent for PLGA. The PLGA/eADF4 composite membranes were developed by using the process of electrospinning. The spinnability of the electrospinning solutions and the physicochemical, mechanical, and thermal properties of the composite membranes were characterized. The addition of eADF4 increased the viscosity of the electrospinning solutions and enhanced both the mechanical characteristics and the thermal stability of the composites. This study demonstrates that PLGA membranes reinforced with recombinant spider silk fibroin are noncytotoxic, significantly enhance cell migration and wound closure, and do not trigger an inflammatory response, making them ideal candidates for advanced wound healing applications.