Rotenone (pesticide and mitochondrial complex I inhibitor) has been associated to induce toxicity in humans and as well as in animals. The present study evaluated the protective role of curcumin against rotenone-induced motor deficits, biochemical and neurochemical alterations. Rotenone was injected subcutaneously at the dose of 1.5 mg/kg for 8 days. Supplementation of curcumin (100 mg/kg/day, p.o.) was started before 15 days of rotenone injection. The effects of curcumin pre-treatment were evaluated by different motor behavioral parameters (pole test, Kondziela’s inverted screen test, inclined plane test, open field test, beam walking test and footprint test). Biochemical and neurochemical alterations were also monitored. Pre-treatment with curcumin reversed the motor impairments, biochemical and neurochemical alterations which were produced by rotenone. Furthermore, curcumin treatment restored the dopaminergic and cholinergic functions. We conclude that curcumin prevent against toxic effect of rotenone and can be beneficial against different neurodegenerative diseases.