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[Display omitted] Recent preclinical studies have shown that resveratrol (RSV), is a promising remedy for osteoporosis owing to its estrogenic, anti-inflammatory, and antioxidant properties. However, RSV has met limited success due to its poor oral bioavailability and inefficient systemic delivery. In this study, we prepared the inclusion complex of RSV with sulfo-butyl ether β-cyclodextrin (SBE-β-CD) to enhance the aqueous solubility of RSV. The in-silico docking studies and Physico-chemical characterization assays were performed to understand the interaction of RSV inside the SBE-β-CD cavity. The in vivo safety assessment of RSV-SBE-β-CD inclusion complex (R-CDIC) was performed in healthy Wistar rats. The efficacy of the inclusion complex against postmenopausal osteoporosis was further investigated in ovariectomized (OVX) rat model. The alteration in the bone micro-architectural structure was evaluated by microcomputed tomographic scanning, serum biochemical estimations, biomechanical strength and histopathological investigation. Administration of RSV-SBE-β-CD inclusion complex was found to be safe and significantly improved micro-architectural deterioration induced by estrogen withdrawal. Results of bone morphometry and biomechanics study further emboldened the efficacy claim of the RSV-SBE-β-CD complex. Thus, the present study demonstrated the efficacy of the RSV-SBE-β-CD inclusion complex for treating osteolytic degradation in osteoporosis. [ABSTRACT FROM AUTHOR]