Diabetes is one of the leading cause of death globally. One of the strategies towards managing diabetes is the antidiabetic drugs which has recorded a huge success but accompanied with different degrees of side effect, hence, the use of natural plants products is encouraged. Several reports of antidiabetic medicinal plants have flooded literature but few has led to identification of active ingredient in such. Cucumis sativus is one of such plants reported to have antidiabetic property but there is little or no data on the active agent. This chapter therefore provides report on the active principle and mechanism of action underlying the antidiabetic activity of C. sativus.