Background Osteoporosis is a metabolic, hereditary, progressive disease characterized by unusual bone production across the skeleton and a loss the bone tissue microstructure and mass. In this experimental study, we scrutinized the antiosteoporosis effect of nimbolide against glucocorticoid (GCs) induced osteoporosis in rats. Methods Swiss albino female rats were employed for the current experiment study and the rats were divided into different groups. Dexamethasone (0.1 mg/kg/day) was used for induction the osteoporosis and the rats were received the different doses of nimbolide (2.5, 5, and 7.5 mg/kg) for the estimation of bone protective effects. The body weight was estimated (initially and finally). Hormones, bone metabolic markers, bone turnover markers, bone structure, biomechanical, histomorphometric dynamic, biochemical markers, and histomorphometric static parameters were analyzed. Results The body weight of GCs group rats considerably suppressed and nimbolide treatment remarkably improved the body weight. Nimbolide treated group exhibited the enhancement of bone metabolic, bone structure markers, and histomophometric dynamic markers, which was suppressed during the GCs‐induced osteoporosis. GCs‐induced osteoporosis rats exhibited the enhancement of procollagen type 1 C‐terminal propeptide (P1CP), carboxy‐terminal crosslinked telopeptide of type 1 collagen (CTX‐1), Dickkopf‐1 (DKK1), tartrate‐resistant acid phosphatase 5b (TRACP 5b), and suppressed the level of bone alkaline phosphatase (BAP), which was reversed by the nimbolide treatment. Nimbolide treatment remarkably improved the level of estradiol and suppressed the level of parathyroid hormone (PTH), which was altered during the osteoporosis. Nimbolide treatment significantly (p < 0.001) improved the level of calcium, magnesium, and phosphorus in the serum and bone tissue. Nimbolide treatment also altered the level of bone metabolic markers and suppressed the level of inflammatory cytokines. Conclusion Based on the findings, we may conclude that nimbolide has antiosteoporosis properties via balancing the bone mass and improving vitamin and hormone levels.