Background: Ancient Indian Ayurvedic literature prescribes Cardiospermum halicacabum as a remedy for rheumatism, lumbago, stiffness of limbs and allied diseases of musculo-skeletal system. Aim: The present study is to investigate the anti-osteoporotic potential of hydro-ethanolic extract of Cardiospermum halicacabum Linn. on human osteoblast-like cells (MG-63) and their phytochemicals are profiled by GC-MS. Materials and methods: Cell proliferation rate was assessed by standard colorimetric MTT assay on human osteoblast-like cells (MG-63). The osteoblastic and osteoclastic activities in MG-63 cell line were determined by assaying of bone markers like Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH). Results: The hydro-ethanolic extract of Cardiospermum halicacabum shows a significant increase in both proliferation and ALP activity in osteoblasts, and decreased LDH leakage in the supernatant of cultured human osteoblast-like cells (MG-63). The GC-MS analysis of hydro-ethanolic extract of C. halicacabum revealed the presence of more than 70 phytoconstituents. Conclusion: Hydro-ethanolic extract of Cardiospermum halicacabum showed a potential influence on osteogenesis and hence its use could be explored as a potential anti-osteoporotic agent.