Abstract: Pyruvic acid (pyruvate plus hydrogen [H+]) is a key of important metabolites in glucose metabolism. Exogenous pyruvate can efficiently improve glucometabolic disorders: mainly preservation of anaerobic glycolysis in cytosol, reactivation of declined oxidative phosphorylation in mitochondria, hence, restoration of the aberrant Warburg effect, enhancement of redox potential status, inhibition of inflammation and apoptosis in addition to depression of advanced glycation end products (AGEs) in tissues. Therefore, pyruvate can protect against diabetes and its organ complications, turning the vicious cycle virtuous in diabetic initiation and development. Pyruvate advantages are incomparable to anions in current medical fluids and hold a potential paramount significance in clinical settings. This review illustrated pyruvate beneficial biomedical properties and their effects on the prevention and treatment of diabetes and diabetic organ complications with the experimental evidence and clinical case reports. It highlights the novel possibility to deal with diabetes by oral pyruvate, the superior choice to resuscitate critical care patients with or without diabetes by pyruvate-enriched fluids and the feasibility to prevent and treat diabetes and its complications with pyruvate-enriched oral rehydration solutions (Pyr-ORS) as a functional beverage in a large population. Attention must be paid to diabetes research with pyruvate and its clinical trials are urgently warranted.Abstract: Pyruvic acid (pyruvate plus hydrogen [H+]) is a key of important metabolites in glucose metabolism. Exogenous pyruvate can efficiently improve glucometabolic disorders: mainly preservation of anaerobic glycolysis in cytosol, reactivation of declined oxidative phosphorylation in mitochondria, hence, restoration of the aberrant Warburg effect, enhanc...Show More