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Biocompatibility, mechanical strength, and osteogenesis properties of three-dimensional scaffolds are critical for bone tissue engineering. In addition, reactive oxygen species accumulate around bone defects and limit the activities of surrounding cells and bone formation. Therefore, the presence of an antioxidant in a bone tissue scaffold is also essential to address this issue. This study aimed to evaluate a composite nanofibrous scaffold similar to the natural extracellular matrix with antioxidant and osteogenic properties. To this end, polylactic acid (PLA)/organophilic montmorillonite (OMMT)/resveratrol (RSV) nanofibers were fabricated using the electrospinning method and characterized. RSV was used as an antioxidant, which promotes osteogenic differentiation, and OMMT was used as a mineral phase to increase the mechanical strength and control the release of RSV. The scaffolds' antioxidant activity was measured using DPPH assay and found 83.75% for PLA/OMMT/RSV nanofibers. The mechanical strength was increased by adding OMMT to the neat PLA. The biocompatibility of the scaffolds was investigated using an MTT assay, and the results did not show any toxic effects on human adipose mesenchymal stem cells (hASCs). Moreover, the Live/Dead assay indicated the appropriate distribution of live cells after 5 days. Cell culture results displayed that hASCs could adhere and spread on the surface of composite nanofibers.Meanwhile, the level of alkaline phosphatase, osteocalcin, and osteopontin was increased for hASCs cultured on the PLA/OMMT/RSV nanofibrous scaffold.Therefore, this study concludes that the RSV-loaded composite nanofibers with antioxidant and osteogenesis properties and appropriate mechanical strength can be introduced for bone tissue regeneration applications.