Zinc (Zn), copper (Cu) and iron (Fe) are essential minerals that are required for a variety of biomolecules to maintain the normal structure, function, and proliferation of cells. These metals can be toxic in excessive amounts, especially in certain genetic disorders. The homeostasis of these trace elements results from a tightly coordinated regulation by different proteins involved in their uptake, excretion and intracellular storage/trafficking. Through the Fenton reaction, Cu and Fe under a non protein-binding condition, can generate various reactive oxygen species, damaging tissues or cells. Abnormal metabolism of Zn, Cu and Fe can lead to several chronic pathogenesis, such as diabetes or diabetic complications. These pathogenic conditions appear to be prevalent in Zn and Cu deficiency, as well as Cu and Fe overload. In the Fe and Cu overloading conditions, Fe and Cu chelating drugs could be used to control diabetes and diabetic complications. The essentiality, toxicity and roles of these metals in the pathogenesis of diabetes and diabetic complications are discussed.