Sesamol (SML) obtained from sesame seeds (Sesamum indicum, Linn, Pedaliaceae) has been used as a traditional health food in India and other countries since a long time. Besides its good antioxidant activity, SML is currently receiving considerable attention in relation to neurological disorders. Therefore, the present study has been designed to explore the protective role of SML in 3-nitropropionic acid (3-NP)-induced neurotoxicity in animals. Male rats were given 3-NP (10 mg/kg) treatment for 14 days. Various behavioral observations (body weight, locomotor activity), oxidative damage (lipid peroxidation, nitrite level, superoxide dismutase, and catalase enzyme), and mitochondrial enzyme complex functions were also assessed in the striatum, cortex, and hippocampal regions of the brain. 3-NP treatment significantly impaired locomotor activity, motor coordination, body weight, oxidative damage, and mitochondrial enzyme complex functions as compared with vehicle-treated groups. SML (5, 10, and 20 mg/kg) pre-treatment significantly improved body weight, locomotor activity, motor coordination, and attenuated oxidative damage in different regions of rat brain. Besides these, SML treatment also significantly improved mitochondrial enzymes in all regions of the brain as compared with the respective control (3-NP) group. The present study suggests that SML could be used as effective agents in the management of Huntington's disease.