Smart scaffolds have a great role in the damaged tissue reconstruction. The aim of this study was developing a scaffold that in addition to its fiber's topography has also content of micro‐RNAs (miRNAs), which play a regulatory role during osteogenesis. In this study, we inserted two important miRNAs, including miR‐22 and miR‐126 in the electrospun polycaprolactone (PCL) nanofibers and after scaffold characterization, osteoinductivity of the fabricated nanofibers was investigated by evaluating of the osteogenic differentiation potential of induced pluripotent stem cells (iPSCs) when grown on miRNAs‐incorporated PCL nanofibers (PCL‐miR) and empty PCL. MiRNAs incorporation had no effect on the fibers size and morphology, cell attachment, and protein adsorption, although viability and proliferation rate of the human iPSCs were increased after a week in PCL‐miR compared to the empty PCL. The results obtained from alkaline phosphatase activity, calcium content, bone‐related genes, and proteins expression assays demonstrated that the highest osteogenic markers were observed in iPSCs grown on the PCL‐miR compared to the cells cultured on PCL and culture plate. According to the results, miR‐incorporated PCL nanofibers could be considered as a promising potential tissue‐engineered construct for the treatment of patients with bone lesions and defects.