Resveratrol is a phytoestrogen, known to serve as an agonist for the estrogen receptor, promoting estrogen-like effects such as neuroprotection and bone growth. Estrogen has been shown to decrease the turnover of bone, prevent bone loss, and increase bone mass. Estrogen replacement therapy is used to decrease bone loss in postmenopausal women which presumably acts by increasing osteoblast activity and decreasing the number and activity of osteoclasts. The present study evaluated the effects of resveratrol on late stage osteogenesis of MC3T3-E1 cells and the feasibility to develop resveratrol loaded poly(caprolactone) nanofibers as scaffolds for bone regeneration. The extent of mineral deposition after exposing cells to different concentrations of resveratrol for 2 and 3 weeks was followed by alizarin red staining. The results demonstrated that resveratrol treated groups irrespective of the concentrations studied showed a significant increase in mineralized matrix deposition compared to the control group at both time points. qRT-PCR studies showed a significant up-regulation of IGF2, RunX2, and osteopontin by resveratrol treated cells. Poly(caprolactone) nanofibers with different resveratrol loadings were prepared by the process of electrospinning. The nanofibers showed a sustained release of resveratrol without a burst effect. The bioactivity of the resveratrol loaded nanofibers was confirmed by the increase in mineralized matrix deposition by cells cultured on resveratrol loaded nanofibers compared to control fibers. In conclusion, the results demonstrate that the resveratrol loaded PCL nanofiber matrix is bioactive and has the potential to serve as an osteogenic biomaterial.