Abstract Here, the role of simvastatin-loaded graphene oxide embedded in polyurethane-polycaprolactone nanofibers for bone tissue engineering has been investigated. The scaffolds were physicochemically and mechanically characterized, and obtained polymeric composites were used as MG-63 cell culture scaffolds. The addition of graphene oxide-simvastatin to nanofibers generates a homogeneous and uniform microstructure as well as a reduction in fiber diameter. Results of water-scaffolds interaction indicated higher hydrophilicity and absorption capacity as a function of graphene oxide addition. Scaffolds’ mechanical properties and physical stability improved after the addition of graphene oxide. Inducing bioactivity after the addition of simvastatin-loaded graphene oxide terminated its capability for hard tissue engineering application, evidenced by microscopy images and phase characterization. Nanofibrous scaffolds could act as a sustained drug carrier. Using the optimal concentration of graphene oxide-simvastatin is necessary to avoid toxic effects on tissue. Results show that the scaffolds are biocompatible to the MG-63 cell and support alkaline phosphatase activity, illustrating their potential use in bone tissue engineering. Briefly, graphene-simvastatin-incorporated in polymeric nanofibers was developed to increase bioactive components’ synergistic effect to induce more bioactivity and improve physical and mechanical properties as well as in vitro interactions for better results in bone repair.