BACKGROUND The need for an anti-osteoporotic agent is in high demand since osteoporosis contributes to high rates of disability or impairment (high osteoporotic fracture), morbidity and mortality. Hence, the present study is designed to evaluate the protective effects of vanillic acid (VA) against bilateral ovariectomy-induced osteoporosis in female Sprague-Dawley (SD) rats. METHODS Forty healthy female adult SD rats were separated in to four groups with sham-operated control with bilateral laprotomy (Sham; n = 10), bilateral overiectomy (OVX; n = 10) group, OVX rats were orallay administrated with 50 mg/kg b.wt of VA (OVX + 50 VA; n = 10) or 100 mg/kg b.wt of VA (OVX + 100 VA; n = 10) for 12 weeks (post-treatment) after 4 weeks of OVX. RESULTS A significant change in the body weight gain was noted in OVX group, while treatment with VA substantially reverted to normalcy. Meanwhile, the bone mineral density and content (BMD and BMC) were substantially improved on supplementation with VA. Also, the bone turnover markers like calcium (Ca), phosphorous (P), osteocalcin (OC), alkaline phosphatase (ALP) and deoxypyridinoline (DPD) and inflammatory markers (IL-1β, IL-6, and TNF-α) levels were markedly attenuated in VA-treated rats. Moreover, the biomechanical stability was greatly ameliorated with VA administration. Both the dose of VA showed potent anti-osteoporotic activity, but VA 100 mg showed highest protective effects as compared with 50 mg of VA. CONCLUSIONS Based on the outcome, we concluded that VA 100 showed better anti-osteoporotic activity by improving BMD and BMC as well as biomechanical stability and therefore used as an alternative therapy for treating postmenopausal osteoporosis.