Background. Osteoporosis is a condition where bones weaken due to a loss in density and quality, making them fragile and more susceptible to fractures, even from minor stress or injury. In this experimental study, we scrutinized the antiosteoporosis effect of phyllanthin against glycocorticoid (GIOP) induced osteoporosis in rats. Methods. SD rats were used in this study and subcutaneous administration of DEX (3 mg/kg) was used for the induction of osteoporosis and rats were treated with phyllanthin and alendronate for 12 weeks. The body weight, femur mass, length, hormones, nutrients, antioxidant, cytokines and bone parameters were estimated. The mRNA expression of HO-1, Nrf2, RANK, RANKL and OPG were estimated. Results. Phyllanthin treatment significantly (p < 0.001) improved the body weight, femur mass and femur length. Phyllanthin significantly (p < 0.001) altered the level of hormones estrodiol, PTH; nutrients such as calcium, phosphorus, magnesium; Bone mineral content (BMC) and bone mineral density (BMD); Bone formation marker like ALP, TRAP, osteocalcin, beta-CTX, BGP, cathepsin K, DPD; Bone parameters viz., Tb.N, BV/TV, Tb.sp, BS/BV, Tb.Th; Bone structure analysis includes maximum load, energy, stiffness, maximum stress, young's modules; oxidative stress parameters such as TBARS, CAT, GPx, GSH, GR; cytokines such as TNF-alpha, IL-1 beta, IL-6, IL-10 and antioxidant marker such as HO-1 and Nrf2. Phyllanthin significantly (P < 0.001) altered the mRNA expression of HO-1, Nrf2, RANK, RANKL and OPG. Conclusion.On the basis of result, we can say that phyllanthin exhibited the antiosteoporosis effect against glucocorticoid-induced osteoporosis in rats via alteration of HO-1/Nrf2 and RANK/RANKL/OPG pathway.