Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/ormitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pinealgland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergeticfunction. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxidedismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of LIPOXYGENASE. Melatonin cancause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibitneurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress.The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseasesrelated to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.