In this work, polyvinyl alcohol (PVA), poly(epsilon-caprolactone) (PCL), and their electrospun PVA/PCL (80/20) hybrid nanofibrous mats were used for the development of active wound dressings. The biocompatibility and therapeutic effects of the developed products were studied by in vitro cell culture and in vivo experimental rat wound model. The release rate measurements by HPLC showed that the PVA nanofibrous sample containing phenytoin sodium (PHT-Na) has a higher level of the drug release compared to the hybrid PVA/PCL (80/20) and PCL nanofibrous mats. A mesenchymal stem cell was seeded on neat as well as drug-loaded PVA nanofibrous mats. The results represented that the mats provide a suitable environment for cell growth and viability. PVA nanofibers containing PHT-Na have a unique performance for fibroblasts and myofibroblasts cells formation and consequently reaching to the remodeling phase and faster healing of the wounds. Also, PHT-Na-loaded electrospun PVA nanofibrous mats showed a remarkable efficiency in wound closure compared with the treatments results from gauze, commercial wound dressing Comfeel(A (R))Plus, and 2 % PHT-Na ointment. Histology analysis showed the formation of epidermis, the lack of necrosis, and accumulation of collagen fibers in dermis for PVA nanofibrous mats containing PHT-Na.