Aim: High glucose (HG) impairs the viability and function of osteoblast, thus causing bone metabolism disorder and osteoporosis. Curcumin is a polyphenolic phytochemical derived from the curcuma longa, and it exhibits anti-inflammatory and antioxidant properties, which associated with cell metabolism. The objective of this study is to investigate the effects and mechanisms of curcumin on HG mediated osteoblast dysfunction. Methods: In the present study, osteoblastic cell was treated with or without curcumin, Nrf2 siRNA interference and JNK inhibitor SP600125. Cell proliferation and apoptosis were assessed by CCK-8 assay, cleaved casepase-3 expression and Annexin V-FITC/PI assay, respectively. Osteoblasts differentiation was detected by ALP activity, osteogenic-specific gene and RUNX2 expression. Immunoblot analysis was used to detect protein expression. Results: The results showed that curcumin enhanced the osteoblast differentiation which are reduced by HG condition via Nrf2 activation and ROS/JNK inhibition. Knock-down of Nrf2 partially blocked curcumin-induced Nrf2 activation and ROS/JNK inhibition, as well as the attenuation of curcumin-induced osteoblast differentiation and survival in HG condition. JNK inhibition impair the positive effect of curcumin in response to HG, which presented a similar result to Nrf2 knock-down. Conclusion: ROS-related JNK phosphorylation might serve as the mechanism for HG-induced apoptosis and Nrf2 activation mediated by curcumin exerted a protective role against osteoblast apoptosis.