Background & Aim: Diabetes mellitus is a metabolic disorder also, is the most important endocrine disease, which leads to an increase in the rate of complications and mortality. Plant medicines (phytotherapies) have a long history as control and treatments for many diseases such as diabetes and up to now, more than 800 kinds of plant medicines have been used as blood glucose reducers.  The World Health Organization has also recommended the use of safer and cheaper plants as an alternative to modern drugs for the control and treatment of diseases. In Iranian and some other country’s traditional medicine, the plant Citrullus colocynthis was used to treat many diseases such as diabetes. The aim of this study was to collect the enough scientific information about the effect of Citrullus colocynthis on control and treatment of diabetes mellitus.
 Material and Methods: The methodology of this study was to search in the international and Iranian scientific sites such as pub med, Iran medex, www.inlm.org and Iranian traditional medicine books in order to collect enough scientific information about the diabetes mellitus and effect of Citrullus colocynthis on reduction of blood glucose and diabetes complications. Then, the results of 31 related papers and books were concluded as a review article.
Results: Many studies worldwide, Iran, Pakistan, Morocco, England, Nigeria, China, Egypt, India and Saudi Arabia, have indicated a significant antihyperglycemic effect with petroleum ether extract of Citrullus Colocynthis fruits. Results of these studies have shown that extract of this fruit can significantly reduce fasting blood glucose, glycosidase hemoglobin, and oxidative stress markers in laboratory animals and otherwise in patients. 
Also, following treatment of the diabetic rats with Citrullus colocynthis pulp extract, their livers showed an improvement in the histological architecture with persistence of the cytoplasmic vacuoles in some hepatocytes.
 Conclusion: According to results of many studies that reviewed, it can be concluded that oral administration of Citrullus Colocynthis extract might reduced blood glucose and improve hepatic functions.