Vindoline, an indole alkaloid present in the leaves of Catharanthus roseus plant, has been recently reported to have insulotropic effects. This present study evaluated the possible hepatoprotective effects of vindoline in a type 2 diabetes mellitus rat model. Diabetes mellitus was induced by exposing rats to 10% fructose water for two weeks followed by a single intraperitoneal injection of 40 mg/kg body weight of streptozotocin (STZ). Rats were randomly divided into six groups (n = 8) and treated daily for 6 weeks with the vehicle via oral gavage, vindoline (20 mg/kg) or glibenclamide (5 mg/kg). Weekly fasting blood glucose (FBG) levels and body weight were measured and recorded. Administration of vindoline significantly (p < 0.05) reduced FBG by 15% when compared to the diabetic controls. Vindoline significantly (p < 0.05) decreased diabetes-induced hepatic injury shown by decreased levels of serum alanine transferase (ALT) (-42%), aspartate aminotransferase (AST) (-42%) and alkaline phosphatase (-62%) compared to the diabetic controls. The oxygen radical absorbance capacity and the activities of superoxide dismutase (SOD) and catalase (CAT) were also improved following treatment with vindoline. The results also showed decreased levels of pro-inflammatory cytokines such as TNF-ɑ by (-41%) and IL-6 (-28%) which may have also contributed to the reduction of serum triglycerides (-65%) in the diabetic group treated with vindoline. Histopathological findings showed improvement of both the hepatic and pancreatic tissues following vindoline treatment. Overall, these findings suggest that vindoline may protect the diabetic hepatic tissue from injury via antioxidant, anti-inflammatory and anti-hypertriglyceredemia mechanisms thereby retarding the development of diabetic complications.