This study evaluated the antioxidant potentials of methanolic extract of Tamarindus indica leaves using in vitro and in vivo assays. reliminary qualitative screening of phytochemicals revealed the presence of alkaloids, flavonoids, saponins, tannins, cardiac glycosides and steroids. The result of the acute toxicity test of the extracts revealed the LD50 to be above 5000 mg/kg through both oral and intra-peritoneal routes. Both the in vitro and in vivo assays were carried out. The reducing power (0.45±0.007 μg/ml) was recorded for T. indica with a difference of 0.77% in comparison to the control and DPPH value (68.10 ± 0.007%) with a significant increase compared to ascorbic acid. The in vivo analysis shows that lipid peroxidation, superoxide dismutase and catalase activities have values of 22.75 ± 9.29 nmol/mg, 1.60 ± 0.03 U/ml and 0.003±0.001 μmol/mg, respectively. The values for superoxide dismutase and lipid peroxidation were significantly different compared to the control (1.48 ± 0.03 U/ml and 24.54 ± 9.29 nmol/mg, respectively) while the value for catalase activity was not significant compared to the control (0.0025 ± 0.001 μmol/mg). The liquid chromatography mass spectrometry revealed the presence of some important metabolite; linoleic acid and quassin, among others, which are antioxidant. Based on the results obtained, the T. indica leaves contain vital metabolites with antioxidant potential that could be useful in health management.