Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder resulting from a selective loss of dopaminergic neurons. The pathogenesis of PD remains incompletely understood, but increasing evidence from human and animal studies has suggested that oxidative damage contributes to the neuronal loss in PD. In this study, we used rotenone (a mitochondrial complex I inhibitor) based cell and Drosophila models that resemble some key pathological features of PD to test whether curcumin, a potent antioxidant compound, derived from the curry spice turmeric, could protect against rotenone-induced neuronal toxicity. We found that curcumin reduced rotenone induced cell death in SH-SY5Y human neuroblastoma cells and alleviated PD-like symptoms in drosophila via reducing the intracellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting the caspase-3/caspase-9 activity. These results suggest that curcumin is a promising therapeutic compound for PD.