As an essential cellular metabolite, alpha-ketoglutarate (AKG) exhibits diverse biological effects, encompassing antioxidant stress response, metabolic stabilization, immune modulation, autophagy promotion, and involvement in epigenetic modification, among others. It is of paramount importance for the normal operation of the organism. Consequently, supplementing AKG holds promise as a safe and effective adjunctive therapeutic approach for safeguarding multiple organs in the human body and promoting as well as maintaining human health. This review summarizes the biosynthesis pathway, administration modalities, action mechanisms, and regulatory and protective effects on various organ diseases of AKG, aiming to provide reference for the basic theoretical research and clinical application transformation of AKG.