Diabetic kidney disease (DKD) is a significant complication of diabetes mellitus, characterized by substantial lipid disturbances, including alterations in triglycerides (TGs), cholesterol (CHOL), sphingolipids, phospholipids (PLs), lipid droplets (LDs), and bile acids (BAs). These lipid metabolism disorders play a crucial role in the pathogenesis of DKD, potentially intertwining with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota, which impacts the liver-kidney axis. The article explores the link between lipid metabolism disruptions and DKD onset, highlighting the importance of understanding these mechanisms for developing new therapeutic strategies. The study characterizes the lipid metabolism changes in DKD, including abnormal TG metabolism, CHOL metabolism, sphingolipid anomalies, PL metabolism, LD accumulation, and BAs metabolism. These changes are associated with reactive oxygen species (ROS) production, oxidative stress, inflammation, and cell death. The mechanisms of lipid metabolic changes in DKD are discussed, focusing on metabolic reprogramming (MR), ferroptosis, lipophagy, and immunomodulation of gut microbiota. The article also reviews conventional drugs and traditional Chinese medicine (TCM) monomers and compound formulas that target lipid metabolism disorders in DKD. Conventional drugs such as atorvastatin, fenofibrate, betulinic acid, liraglutide, α-lipoic acid, and adiponectin receptor agonist AdipoRon are highlighted for their potential in improving lipid metabolism and delaying DKD progression. TCM monomers and compound formulas, such as berberine, breviscapine, microvascular endothelial differentiation gene-1 (MDG-1), proteoglycan FYGL, notoginsenoside R1, triptolide, mulberry extract, Panax japonicus C.A. Meyer (PJ), resveratrol, cordyceps cicadae polysaccharides (CCP), and magnesium lithospermate B (MLB), are also discussed for their therapeutic effects on DKD. The authors emphasize the need for further research to clarify the specific targets of interventions and to understand the mechanisms of action of natural drugs. They suggest that a multidisciplinary approach, combining computational and experimental methods, can provide deeper insights into the pathophysiology of DKD and enhance therapeutic developments. The article concludes by highlighting the importance of merging computational and experimental methods in biomedical research to advance the understanding and treatment of DKD.Diabetic kidney disease (DKD) is a significant complication of diabetes mellitus, characterized by substantial lipid disturbances, including alterations in triglycerides (TGs), cholesterol (CHOL), sphingolipids, phospholipids (PLs), lipid droplets (LDs), and bile acids (BAs). These lipid metabolism disorders play a crucial role in the pathogenesis of DKD, potentially intertwining with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota, which impacts the liver-kidney axis. The article explores the link between lipid metabolism disruptions and DKD onset, highlighting the importance of understanding these mechanisms for developing new therapeutic strategies. The study characterizes the lipid metabolism changes in DKD, including abnormal TG metabolism, CHOL metabolism, sphingolipid anomalies, PL metabolism, LD accumulation, and BAs metabolism. These changes are associated with reactive oxygen species (ROS) production, oxidative stress, inflammation, and cell death. The mechanisms of lipid metabolic changes in DKD are discussed, focusing on metabolic reprogramming (MR), ferroptosis, lipophagy, and immunomodulation of gut microbiota. The article also reviews conventional drugs and traditional Chinese medicine (TCM) monomers and compound formulas that target lipid metabolism disorders in DKD. Conventional drugs such as atorvastatin, fenofibrate, betulinic acid, liraglutide, α-lipoic acid, and adiponectin receptor agonist AdipoRon are highlighted for their potential in improving lipid metabolism and delaying DKD progression. TCM monomers and compound formulas, such as berberine, breviscapine, microvascular endothelial differentiation gene-1 (MDG-1), proteoglycan FYGL, notoginsenoside R1, triptolide, mulberry extract, Panax japonicus C.A. Meyer (PJ), resveratrol, cordyceps cicadae polysaccharides (CCP), and magnesium lithospermate B (MLB), are also discussed for their therapeutic effects on DKD. The authors emphasize the need for further research to clarify the specific targets of interventions and to understand the mechanisms of action of natural drugs. They suggest that a multidisciplinary approach, combining computational and experimental methods, can provide deeper insights into the pathophysiology of DKD and enhance therapeutic developments. The article concludes by highlighting the importance of merging computational and experimental methods in biomedical research to advance the understanding and treatment of DKD.