Diabetes mellitus is a disorder resulting from a lost in control of blood glucose level by insufficient insulin release (type 1), impaired insulin function, or insulin resistance (type 2). The main etiology for mortality and a great percent of the morbidity in patients with diabetes is cardiovascular disease. In addition to hyperglycemia, enhanced oxidative stress plays a major role in the pathogenesis of diabetes. Although reactive oxygen species (ROS) are known to be mediators of intracellular signaling pathways under physiological conditions, excessive production of ROS can be detrimental to the cells as a result of increased oxidative stress and thereby cellular dysfunction. Hence, well-tuned, balanced, and responsive antioxidant systems are vital for proper regulation of the redox status of the cells. Studies have reported valuable effects of antioxidant agents, including trace elements, on diabetes-induced cardiovascular system dysfunctions, either directly or indirectly. Thus, several approaches have been carried out to either diminish an elevated ROS production or improve the endogenous levels of antioxidants. Indeed, reduced fatty acid oxidation and use of trace elements in treatment strategies result in promising prevention hints for diabetes-induced cardiovascular dysfunctions. Our scope here is to review the important role of antioxidants, particularly selenium, as cardioprotective agents in several types of disease states including diabetes, presenting our research results on cardiac function by using experimental animal models for diabetes. Although the paradigm that inhibiting overproduction of superoxides and peroxides would prevent cardiac dysfunction diabetes-induced damage has been difficult to verify using conventional antioxidants such as selenium, of special note is that its role as hyperglycemia controller, insulin sensitizer, or antioxidant therapy remains to be further explored as well as the effect of hypolipidemic therapy.