Background and Aims: Citrullus colocynthis (Schrad) fruit is a toxic herbal medicine extensively used by traditional herbalists for the treatment of diabetes in several parts of Iran. Clinical investigation of its efficacy and its toxicity in diabetic patients is of importance.

Materials and Methods: A 2-month randomized double blind clinical trial was conducted in 50 type II diabetic patients in two matched groups. One group (n=25) received 100 mg Citrullus colocynthis capsule 3 times a day plus standard therapy, while the control group (n=25) received placebo plus standard therapy. The patients were visited monthly and glycosylated hemoglobin (HbA1c), fasting blood glucose, total cholesterol, LDL and HDL, triglyceride, SGOT, SGPT, ALK, BUN, serum creatinine levels were determined at the beginning and the end of the study after two months.

Results: There was significant decrease in HbA1c and fasting blood glucose level in citrullus colocynthis fruit treated patients after two months as compared to beginning of the treatment and also as compared to placebo group. Serum lipid level was not changed significantly. The liver enzyme level and creatinine level in blood was not changed significantly in citrullus colocynthis fruit treated patients. No serious side effect was observed except mild diarrhea in 10% of patients, that, subsided with continuation of treatment.