Metallothioneins (MTs) are a family of low molecular weight proteins with a high cysteine and metal ion content. They are found in most cells and tissues and can be induced by a number of substances, including various forms of oxidative stress. MTs play a central role in essential trace element homeostasis and in metal detoxification. Because of their peculiar structure, characterized by a large content of thiol groups, MTs also act as a potent antioxidant by protecting against various injuries resulting from reactive oxygen (ROS) or nitrogen species (RNS). In this review, the involvement of MT in the protection of DNA against oxidative stress is discussed.