The treatment for the bone diseases or defects such as tumor ablation, bone cysts and osteolysis were still challenging in clinical applications. Recently, the bone tissue engineering has emerged as a potential option for the treatment of bone defects. In this study, the nanofibrous composite scaffold consisting of polyurethane, olive oil, honey and propolis were fabricated through electrospinning method. The morphology of the nanofibrous scaffold indicated that nanofibers diameters were reduced with the addition of olive oil, honey and propolis into the Polyurethane (PU). The contact angle measurements showed that the behavior of PU/olive oil was found to hydrophobic (114° ± 1.528) and the PU/olive oil/honey/propolis scaffold rendered hydrophilic behavior (60° ± 1.528). FTIR and TG analysis revealed the interactions of PU with olive oil, honey/propolis and increased thermal stability of the composites. Atomic Force Microscopy (AFM) analysis displayed reduced surface roughness of the fabricated nanocomposite (PU/olive oil—469 nm and PU/olive oil/honey/propolis—449 nm) than the pristine PU (576 nm). The incorporation of olive oil, honey, and propolis resulted in the enhancement of the tensile strength (PU/olive oil—12.91 MPa and PU/olive oil/honey/propolis—14.346 MPa) compared with the pristine PU (7.12 MPa) as revealed in the mechanical testing. The blood clotting time of PU/olive oil (Activated partial thromboplastin time (APTT)—175 ±4 s and Partial thromboplastin time (PT)—103.3 ±3.512) was enhanced than pristine PU suggesting its improved anticoagulant behavior. Further, the developed scaffold showed low hemolytic index percentage (PU/olive oil—1.41% and PU/olive oil/honey/propolis—0.95%) than the control (2.48%) indicating its safety with RBC. Cytotoxicity test of the electrospun scaffold with human dermal fibroblast (HDF) cells using 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H tetrazolium assay demonstrated the non‐toxic and enhanced cell viability rates of HDF cells in developed scaffold than the pristine PU. Hence, the PU/olive oil/honey/propolis nanocomposite possessing better mechanical, physio‐chemical and biological properties might serve as a plausible candidate for bone tissue engineering. POLYM. COMPOS., 2018. © 2018 Society of Plastics Engineers