Natural compounds are alternative agents that have therapeutic potential for preventing and treating osteoporosis. Traditionally, sanguinarine has been used clinically due to its diverse biological properties, including antimicrobial, anti‑inflammatory and anticancer effects. Recently, for the first time, it was reported that sanguinarine inhibits osteoclast differentiation and bone resorption by suppressing the tumor necrosis factor ligand superfamily member 11‑induced nuclear factor‑κB and extracellular signal‑regulated kinase signaling pathways in vitro. Therefore, the present study further investigated the pharmacological effect of sanguinarine on osteoporosis in vivo. Micro‑computed tomography and histomorphometry analysis demonstrated that sanguinarine, at low and high concentrations, prevents ovariectomy (OVX)‑induced bone loss. In addition, further investigation of the cellular response in vivo revealed that sanguinarine inhibited osteoclastic bone resorption and promoted osteoblastic bone formation in a dose‑dependent manner. Therefore, the present study demonstrated that sanguinarine protected mice from OVX‑induced osteoporosis by modulating bone remodeling, indicating that sanguinarine may have potential in the treatment of osteoporosis.