This study evaluates the antioxidative effect of dehydroepiandrosterone (DHEA) treatment on 3-nitropropionic acid (3-NPA)-induced oxidative stress in striatal and brain cortex synaptosomes. The oxidative derangement was confirmed by a high level of lipid peroxidation products and protein carbonyls, as well as by an enhanced superoxide dismutase activity (p < 0.001). These changes were partially prevented by DHEA. Moreover, 3-NPA induced a drop in succinate dehydrogenase activity, while DHEA treatment restored the succinate dehydrogenase activity. These results show that DHEA reduces oxidative stress in synaptosomes isolated from the brain of 3-NPA-treated rats, and they suggest this neurosteroid may protect mitochondrial and maintain synaptic integrity against damage induced by this acid.