Diabetes is a disease characterized by high blood glucose due to the abnormal response of the cells in the body on produced insulin or insulin resistance. Indeed, the treatment for diabetes mellitus lasts for a lifetime and causes various side effects, such as headache, hypoglycemia, vomiting, and gastrointestinal symptoms. Interestingly, Dragon fruit has potent antidiabetic activity and without side effects. Thirty Wistar mice were included in the study. Alloxan with a dose of 150 mg/kg was injected intraperitoneally to all groups except the standard control group. Mice with blood glucose levels higher than 200 mg/dL were considered diabetic and employed throughout the study. Mice were divided into five groups: standard control group without alloxan, diabetic control group with alloxan, treatment group of 100 mg/kg and 300mg/kg H. polyrhizus peel extract, and positive control group with 600 µg/kg glibenclamide. All treatments were given orally. Blood glucose level was checked on day 1, 7, and 14 on all groups using Accu-check instant glucometer. This study revealed that administration of alloxan to the diabetic control group significantly increased blood glucose level compared to the normal control group on day-1, 7, and 14 (P < 0.05). In addition, administration of H. polyrhizus peel extract and glibenclamide effectively decreases blood glucose levels, especially on day-7 and 14 compared to the control group (P<0.05).