The antidiabetic properties of Tiliacora triandra ethanol extract in diabetic rats induced with high-fat diet (HFD)/streptozotocin (STZ) was investigated. Rats were fed with HFD for 4 weeks to induced insulin resistance, and thereafter administered with 35 mg/kg of STZ to induce diabetes. Diabetic rats received 100 and 400 mg/kg of T. triandra daily for 30 days. The body weight, blood glucose level, food and fluid intake were monitored. Furthermore, biochemical and histological assessment was performed to evaluate the hypoglycemic effect of the extract in the treated rats. T. triandra significantly decreased the blood glucose level, increased the body weight and insulin secretion. Furthermore, T. triandra attenuated hyperlipidemia, improved liver and kidney functions of treated diabetic rats. Thus, T. triandra could effectively attenuate diabetes and it complications. Practical applications: Tiliacora triandra is a common vegetable consumed in Thailand and Laos. It is traditionally employed in the treatment of fever, cancer, malaria, and diabetes. The extract from the aerial part was investigated for its antidiabetic properties. The results obtained provides important pharmacological information that supports the use of T. triandra in management of diabetes.