Osteoporosis is a metabolic bone disease characterized by an imbalance between osteoclastic bone resorption and osteoblastic bone formation, ultimately resulting in reduced bone mass and structural fragility. Inflammatory stress is known to impair osteoblast differentiation and function, thereby contributing to bone loss. SA, a member of the Cucurbitaceae family, has been reported to exhibit various pharmacological activities, including anti‑inflammatory, antioxidant, and anti‑obesity effects; however, its role in osteoblast differentiation remains largely unexplored. In this study, a 70% ethanol extract of SA and its ethyl acetate fraction were evaluated for their protective effects against lipopolysaccharide (LPS)–induced osteoblast dysfunction. Among six compounds isolated from SA, Compound 1 showed the most pronounced restoration of osteoblast function under inflammatory conditions, as demonstrated by enhanced alkaline phosphatase (ALP) activity and increased Alizarin Red S (ARS) staining. Subsequent experiments focused on Compound 1, which alleviated LPS‑induced osteoblast dysfunction and reduced inflammatory responses in MC3T3‑E1 cells. Conclusively, these findings indicate that Compound 1 from SA exerts protective effects against LPS‑induced inflammatory stress in osteoblasts and may represent a promising candidate for preventing inflammation‑associated bone disorders such as osteoporosis.