Solanum anguivi fruit saponin has antidiabetic property via interference with cellular energy metabolism and inhibition of reactive oxygen species (ROS) generation. In the current study, brain specific in vitro anti-oxidant role of S. anguivi saponin was investigated in the P2 synaptosomal fraction of rat brain. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, S. anguivi saponin concentration- dependently (10-200 µg/ml) reversed Fe2+ and sodium nitroprusside- induced decrease in mitochondrial activity via inhibition of ROS production, ROS-induced oxidation of protein and non-protein thiol-containing molecules and lipid peroxidation as measured by thiobarbituric acid reactive substances levels. Conclusively, S. anguivi fruit saponin represents a class of natural compounds with the ability to reverse synaptosomal disruption, loss of mitochondrial integrity and function often associated with the progression of Huntington's disease, Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis diseases.