A common side effect of prolonged glucocorticoid therapy is osteoporosis which is the most common cause of secondary osteoporosis. The aim of our study was to investigate the potential anti-osteoporotic effect of Vigna radiata (V. radiata) and Lepidium sativum (L. sativum) extracts in prednisolone acetate (PA)-induced osteoporotic rats. Rats were divided into 2 main groups (30 males and 30 females). Each main group was randomly divided into 5 equal subgroups. Rats of subgroup I were served as normal control and received the vehicle. Rats of subgroup II (osteoporotic control) were co-administered PA at 5 mg/kg and the vehicle. Subgroup III was administered with alendronate sodium (3 mg/kg) and served as a reference control. Subgroups IV and V were administered with V. radiata and L. sativum extracts (500 mg/kg), respectively. Body weights of all rats were measured at 3, 6, 9 and 12 weeks after PA, reference and extracts administration. At the end of the experimental period, serum samples and femur bones were examined. PA administration significantly reduced body weight gain, serum levels of calcium (Ca2+), Phosphorous (P) and alkaline phosphatase (ALP), as well as, femur weight and thickness and femur contents of Ca2+ and P of male and female rats. Administration of L. sativum extract (500 mg/ kg) significantly protected against the reduction in the serum and bone levels of Ca2+ and P and femur physical parameters of PA-exposed male and female rats. Histopathological results supported protective effect of the extract. Our findings suggest a potential protective role of L. sativum against PA-induced osteoporosis in male and female rats. In addition, V. radiata did not produce any considerable protection against the deleterious effect of PA on the bone of male and female rats. Key words: Lepidium sativum; Vigna radiata; osteoporosis; rats