Diabetes mellitus has surfaced as a serious global public health issue. Previous research in our laboratory has demonstrated a link of knockouts and(or) overexpression of glutathione peroxidase-1 (Gpx1) and Cu,Zn-superoxide dismutase (Sod1) to increased risks of diabetes in mice. This research explores if and how GPX1 and SOD1 regulate functional expression of metal transporters in exerting their impacts on diabetes. The first study investigates the impact of these enzyme regulations on the expression of metal and glucose transporters in tissues of different mouse models (Gpx1-KO, Gpx1-OE, Sod1-KO, dKO), revealing the complex interplay between antioxidant enzymes and mRNA and protein expression levels of various metal and glucose transporters. The second study delves into the responses of zinc uptake in pancreatic islets to different stimulations within the framework of Gpx1 regulation. The findings of this study demonstrate that both the knockout and overexpression of the Gpx1 gene lead to the downregulation of various zinc transporter genes in islet cells, and when Gpx1 is overexpressed in mouse islets, a notable decrease in zinc fluorescence is observed during the process of insulin secretion, providing novel insights into two major antioxidant enzymes’ regulation on metal transporter gene expressions and functions.