Salacia oblonga (S. oblonga) is a component of several antidiabetic medications in alternative and folklore medicine. An evaluation of the hydroalcoholic root extract of S.oblonga (SOE) on the hepatocellular and pancreatic environment in the diabetic (Streptozotocin) rodent model was designed. SOE was fed in two doses for a period of 16 weeks. Regeneration of endocrine pancreas, significant increase in hepatic and pancreatic Vitamin C, reduced Glutathione (GSH), Protein thiols (PT) and decrease in Malondialdehyde (MDA measured as TBARS) and Carbonyl proteins (CP) were observed on treatment with SOE. Conversely, there was also an increase in alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT). Corroborating the above findings, histopathological examination of the liver and pancreatic tissue showed disrupted architecture in treated rats. It may be suggested that SOE has a sustained hepatic antioxidant effect and improved β-cell structure and function in diabetic rats, but the higher dose was mildly toxic to hepatocytes necessitating an exercise of caution in using SOE for therapy for prolonged periods.