Citrullus colocynthis whole, also known as bitter cucumber, is a fruit-bearing plant sometimes used medicinally. Citrullus colocynthis is an annual plant that grows in the south, center, and east areas of Iran. It is recognized by different pharmacologic activities in traditional Iranian medicine (TIM) (i.e., purgative, anti-inflammatory, antidiabetic, analgesic, hair growth-promoting, abortifacient, and antiepileptic. Citrullus colocynthis is used to treat diabetes, since it may be able to induce insulin secretion from the pancreas after supplementation, while reducing blood glucose and improving lipid levels. In a randomized clinical trial, HbA1c and fasting blood glucose levels were decreased in patients using 300 mg of C. colocynthis dry fruit powder daily for 2 months. In another trial, intake of 300 mg of powdered seed can lower the triglyceride and cholesterol concentration significantly in nondiabetic hyperlipidemic patients. Preliminary evidence suggests a topical application of Citrullus colocynthis may stimulate hair growth, with an effect comparable to finasteride, a male pattern baldness drug. More evidence is needed to confirm this effect. Aqueous and methanol extracts of colocynth showed high antimicrobial activity against Escherichia coli, Staphylococcus aureus, and other bacteria. Extracts of fruits, leaves, roots and stems were also found to be potentially usable against many Gram positive bacilli and fungi such as Aspergillus fumigatus, Aspergillus flavus, and Mucor species. Even low doses (100mg, taken three times) of Citrullus colocynthis can cause diarrhea, while higher doses (1,500 mg) can cause colonic inflammation and rectal bleeding. These side-effects stop once supplementation is ceased. Since the bioactive compounds in Citrullus colocynthis are still unknown, and even low-dose supplementation is associated with intestinal side-effects, Citrullus colocynthis is not recommended for oral supplementation. There are no approved products of C. Colocynthis.