The goal of the current study was to develop an asymmetric guided bone regeneration (GBR) membrane benefiting from curcumin and aspirin. The membrane was prepared using electrospinning technique and then was physic-chemically characterized by the conventional methods. The release profile of aspirin from the prepared membrane was also measured by ultraviolet spectrophotometry. Also, the antibacterial activities of the membrane was evaluated. We also assessed the in vitro effects of the prepared membrane on the biocompatibility and osteogenic differentiation of dental pulp stem cells (DPSCs), and evaluated in vivo bone regeneration using the prepared membrane in the defects created in both sides of the dog's jaw by histology. The results from the characterization specified that the membrane was successfully prepared with monodispersed nanosized fibers, uniform network shaped morphology, negative surface charge and sustained release platform for aspirin. The membrane also showed antimicrobial effects against all tested bacteria. The presence of curcumin and aspirin in the asymmetric membrane enhanced osteogenic potential at both transcriptional and translational levels. The results of the animal test showed that the test area was completely filled with new bone after just 28 days, while the commercial membrane area remained empty. There was also a soft tissue layer above the new bone area in the test side. We suggested that the prepared membrane in this work could be used as a GBR membrane to keep soft tissue from occupying bone defects in GBR surgeries. Besides, the surgeries can be benefited from antibacterial activities and bone healing effects of this novel GBR membrane while, simultaneously, promoting bone regeneration.