Diabetes is a widespread disease, and its development and toxic effects on various organs have been attributed to increased oxidative stress. Metallothionein (MT) is a group of intracellular metal-binding and cysteine-rich proteins, being highly inducible in many tissues. Although it mainly acts as a regulator of metal homeostasis such as zinc and copper in tissues, MT was found to be a potent antioxidant and adaptive (or stress) protein to protect cells and tissues from oxidative stress. Studies showed that zinc-induced or genetically enhanced MT synthesis in the pancreas prevented the development of spontaneous or chemically-induced diabetes. Genetically or pharmacologically enhanced MT expression in various organs including heart and kidney provided significant protection from diabetes-induced organ dysfunction such as cardiomyopathy and nephropathy. These studies suggest that MT as an adaptive protein can prevent both diabetes development and diabetic complications. This mini-review will thus briefly describe MT's biochemical features and then summarize the data on the protective effect of MT against diabetes and diabetic complications. In addition, the coordinative role of MT with zinc in the prevention of diabetes and its complications will also be discussed.