Glucose-induced reactive oxygen species are associated with diabetic hepatotoxicity. This study focuses on anti-glycemic and anti-hepatotoxic effects of mangosteen vinegar rind (MVR) on high-fat diet (HFD) /streptozotocin (STZ) induced diabetic mice. Male ICR mice were given a HFD for five weeks, followed by a single intraperitoneal injection of STZ 30 mg/kgBW except in the normal control group. After five weeks, based on fasting blood glucose, all mice were randomly divided into five groups (n=6), normal control, diabetic control and diabetic groups who were treated with MVR 100, 200 mg/kg BW and Glibenclamide 60 mg/kg BW for one week. After the treatment, glycogen content, oxidative damage (malondialdehyde, MDA), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) were measured in liver tissues. We found that treatment with MVR and Glibenclamide to HFD/STZ-induced diabetic mice significantly reduced plasma glucose, plasma and hepatic lipid profile (P<0.05). Increased hepatic glycogen content indicates improvement of insulin sensitivity. Moreover, oxidative damage markers and anti-oxidant activity were ameliorated in MVR- and Glibenclamide-treated groups compared to the diabetic control group. MVR enriched phenolic content (74.67±1.73 mg GAE/g dry weight) and ensured a high antioxidant potential (303.32+20.54 mmol/L TEAC/g dry weight, IC50=391.24±26.42 mmol/L TEAC/g dry weight) acting as hepatoprotective agents against oxidative damage. These findings suggest that MVR possesses potent anti-glycemic and hepatoprotective effects by reducing metabolic markers, oxidative stress markers with an improvement in hepatic glycogen level and anti-oxidant enzyme activities of HFD/STZ-induced type II diabetic mice.