Diabetic kidney disease (DKD) is a glomerular disease caused by metabolic disorders that impair renal cell function. Mitochondria play a crucial role in substance metabolism through oxidative phosphorylation to generate ATP. Metabolic reprogramming, a compensatory mechanism to meet energy needs, significantly influences the pathophysiological progression of DKD. Alterations in kidney metabolism lead to abnormal signaling molecule expression, oxidative stress, inflammatory responses, apoptosis, and irregular autophagy, ultimately resulting in renal fibrosis and insufficiency. This review highlights the impact of mitochondrial metabolic reprogramming on DKD pathogenesis, emphasizing the regulation of metabolic regulators and downstream signaling pathways. Therapeutic interventions targeting renal metabolic reprogramming have the potential to delay DKD progression. The findings underscore the importance of focusing on metabolic reprogramming to develop safer and more effective therapeutic approaches. Key points: - Metabolic reprogramming involves changes in cellular metabolic pathways to support cell growth and proliferation. - It is characterized by mitochondrial biosynthesis dysfunction, increased glycolysis, and abnormal lipid and amino acid metabolism. - Oxidative stress, inflammatory damage, abnormal autophagy, and apoptosis caused by metabolic disorders contribute to DKD and renal fibrosis. - Current treatments for DKD can slow disease progression but have adverse effects and do not prevent renal failure. - Newer hypoglycemic agents like SGLT2 inhibitors and GLP-1 agonists can delay DKD progression by regulating metabolic reprogramming. - Further research is needed to understand the mechanisms of these drugs and their impact on metabolic reprogramming. - Therapeutic strategies targeting metabolic reprogramming and restoring normal mitochondrial function show promise for managing DKD.Diabetic kidney disease (DKD) is a glomerular disease caused by metabolic disorders that impair renal cell function. Mitochondria play a crucial role in substance metabolism through oxidative phosphorylation to generate ATP. Metabolic reprogramming, a compensatory mechanism to meet energy needs, significantly influences the pathophysiological progression of DKD. Alterations in kidney metabolism lead to abnormal signaling molecule expression, oxidative stress, inflammatory responses, apoptosis, and irregular autophagy, ultimately resulting in renal fibrosis and insufficiency. This review highlights the impact of mitochondrial metabolic reprogramming on DKD pathogenesis, emphasizing the regulation of metabolic regulators and downstream signaling pathways. Therapeutic interventions targeting renal metabolic reprogramming have the potential to delay DKD progression. The findings underscore the importance of focusing on metabolic reprogramming to develop safer and more effective therapeutic approaches. Key points: - Metabolic reprogramming involves changes in cellular metabolic pathways to support cell growth and proliferation. - It is characterized by mitochondrial biosynthesis dysfunction, increased glycolysis, and abnormal lipid and amino acid metabolism. - Oxidative stress, inflammatory damage, abnormal autophagy, and apoptosis caused by metabolic disorders contribute to DKD and renal fibrosis. - Current treatments for DKD can slow disease progression but have adverse effects and do not prevent renal failure. - Newer hypoglycemic agents like SGLT2 inhibitors and GLP-1 agonists can delay DKD progression by regulating metabolic reprogramming. - Further research is needed to understand the mechanisms of these drugs and their impact on metabolic reprogramming. - Therapeutic strategies targeting metabolic reprogramming and restoring normal mitochondrial function show promise for managing DKD.