This study evaluated the in- vitro antioxidant, phytochemical constituents and hepato-renal protective efficacy of Senna siamea methanolic extract in arsenic-induced oxidative stress. The results of this study show that S. siamea has strong antioxidant potentials against 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2’azinobis (3 ethylbenzothiazoline-6-sulphonic acids) (ABTS) radicals. The extract scavenges nitric oxide radicals and has strong ferric reducing power. It also inhibited the induction of lipid peroxidation and α-amylase activity in a concentration-dependent manner. Administration of arsenic to rats induced a significant increase in the levels of alanine aminotransferase, aspartate aminotransferase, cholesterol, urea, creatinine, and triglycerides in the plasma, while it decreased superoxide dismutase, glutathione and catalase activities in the liver and kidney. It also significantly reduced the levels of white blood cells, red blood cells, platelet and lymphocytes in the blood. However, rats pretreated with S. siamea extract before arsenic administration significantly reversed all these arsenic-induced changes. Histological observations showed varying degrees of liver damage in the arsenic group that was untreated, while the pre-treatment with S. siamea extract significantly improved the general histoarchitecture of the liver. The phytochemical constituents of the extract were determined, the gas-chromatography analysis revealed the possible presence of oxalic acid, barakol, kaempferol, betulin while total phenolics content, crude protein, crude fat, crude fibre are in considerable amount in the plant This study demonstrated that S. siamea extract has antioxidant potentials and ameliorates arsenic-induced hepato-renal toxicity, the effectiveness of S. siamea as a medicinal plant could be due to the presence of various phenolics and antioxidant compounds in the plant.