Background: The fruit of Lycium cliinense (LC), one of the most popular natural materials, has been used to counter the effects of musculoskeletal diseases in oriental medicine. In particular, this fruit is known to have antiaging effects, which is of significant interest to the research community. The purpose of our investigation was to observe and confirm the ameliorative effect of LC on osteoporosis, which was verified in this in vivo study. Methods: Female ICR mice aged 5 weeks were surgically ovariectomized (OVX) to induce osteoporosis. After 7 weeks of induction, oral administration with I mg/kg and 100 mg/kg LC was continued for 6 weeks. At the end of the experiment, the levels of bone mineral content (BMC) and bone mineral density (BMD) were estimated by dual-energy X-ray absorptiometry. Hematoxylin and eosin staining was performed; additionally, serum osteocalcin and calcium concentrations were analyzed. Results: LC treatment significantly reduced the deterioration of BMC and BMD compared with OVX mice. Histological analysis showed that LC ameliorated osteoporosis including the hypertrophy of the epiphyseal plate. Additionally, decreased serum osteocalcin as well as the calcium levels recovered following the administration of LC. Conclusion: These results demonstrated that LC ameliorates osteoporosis in OVX mice by improving several important parameters including BMC, BMD, and bone-turnover markers such as osteocalcin and calcium levels in serum. Copyright (C) 2017, the Chinese Medical Association. Published by Elsevier Taiwan LLC.