Diabetes mellitus (DM) represents a global health and economical problem. Many patients with DM in Asia, South America, India and East Africa have traditionally used the water extract of unripe fruits of Momordica charantia (bitter melon) as some form of complementary and alternative medicine. Studies of laboratory animals have shown the beneficial blood-glucose lowering and anti-diabetic effects of this remedy. Some oral components that bring lower blood glucose level have been isolated : charantin (sterol glycosides), charantin (polypeptide) and cucurbine-type triterpenes. Part of their actions are related to AMP-activated kinase and repression of the oxidative stress that is increased in DM. Most clinical reports are not fully convincing due to the lack of randomized control studies. The present article reviews the pharmacological and clinical effects of bitter melon with special emphasis on the anti-diabetic effects, and some effects that would require caution in the context of human trials.