Most existing bone repair implants in clinical usage require surgical removal after healing or is left within the patient for lifetime. Development of a bio-degradable substitute that mimics natural bone in terms of osteoconduction and osteoinduction may allow better results. The present research focuses on incorporation of bioactive agents namely Aloe vera (AV) and Silk fibroin (SF) with 4% Hydroxyapatite (HA) in the poly (lactic acid-co-caprolactone) (PLACL) to fabricate PLACLAV-SF-HA (4%) nanofibrous scaffolds by electrospinning which can afford close biomimicry to natural bone constitution. Morphology, composition, hydrophilicity and mechanical properties of the electrospun PLACL-AV-SF-HA (4%) nanofibrous scaffold along with other controls namely PLACL, PLACL-AV-SF, PLACL-AV-SF-HA (2%) nanofibrous scaffolds were examined by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle and tensile tests, respectively. Human mesenchymal stem cells cultured on PLACL-AV-SF-HA (4%) nanofibrous scaffolds showed significant increments in cell proliferation, osteogenic differentiation, osteocalcin expression and mineral deposition in comparison with different controls. Obtained results highlight the synergistic effect of osteoinductive property of Aloe vera along with osteoconductive hydroxyapatite in enhancing the differentiation and biological performance of human mesenchymal stem cells to osteoblasts with suitable mechanical support provided by silk fibroin, proving PLACL-AVSF-HA (4%) biocomposite to be a highly ideal nanofibrous scaffold for osteoregeneration related therapeutics.