Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. It is the leading cause of end-stage renal disease (ESRD) globally, resulting from chronic hyperglycemia, oxidative stress, and inflammation. Early detection relies on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment emphasizes glycemic control, blood pressure regulation, and nephroprotective agents like ACE inhibitors, ARBs, SGLT2 inhibitors, and GLP-1 receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on strict glycemic and hypertension control to slow disease progression. Despite advances, DKD remains a leading cause of ESRD, highlighting the need for new biomarkers and treatments. DKD pathogenesis involves structural changes, hyperfiltration, epithelial-mesenchymal transition (EMT), inflammation, lipotoxicity, organelle dysfunction, and vascular dysfunction. Structural changes include glomerular hypertrophy, GBM thickening, and tubular injury. Hyperfiltration leads to tubular hypoxia and fibrosis. EMT contributes to fibrosis through TWIST1, SNAI1, and YAP1. Inflammation and oxidative stress create a vicious cycle, with neutrophil extracellular traps (NETs) exacerbating GEC injury. Lipotoxicity involves lipid accumulation and organelle dysfunction, while mitochondrial dysfunction and vascular changes further impair kidney function. Epigenetic changes, including metabolic memory, also play a role in disease progression. Diagnosis of DKD involves persistent albuminuria, reduced eGFR, and the presence of diabetic retinopathy. The 2012 KDIGO guidelines classify albuminuria into three categories. Screening should begin at DM diagnosis and be repeated annually. Kidney biopsy is rarely used but helps in histological classification. Management of DKD includes glycemic control, lipid management, blood pressure control, and dietary restrictions. Glycemic control is crucial, with HbA1c targets individualized based on CKD severity. SGLT2 inhibitors and metformin are first-line therapies. Lipid management involves statins, ezetimibe, and PCSK-9 inhibitors. Blood pressure control targets <120/80 mmHg for CKD patients. Sodium and protein intake should be restricted to reduce albuminuria and slow CKD progression. Nephrotoxic agents should be used cautiously to avoid further renal damage. Combination therapies targeting multiple pathways may improve outcomes. Emerging therapies, including anti-inflammatory and organelle-targeted treatments, offer promising avenues for DKD management.Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. It is the leading cause of end-stage renal disease (ESRD) globally, resulting from chronic hyperglycemia, oxidative stress, and inflammation. Early detection relies on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment emphasizes glycemic control, blood pressure regulation, and nephroprotective agents like ACE inhibitors, ARBs, SGLT2 inhibitors, and GLP-1 receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on strict glycemic and hypertension control to slow disease progression. Despite advances, DKD remains a leading cause of ESRD, highlighting the need for new biomarkers and treatments. DKD pathogenesis involves structural changes, hyperfiltration, epithelial-mesenchymal transition (EMT), inflammation, lipotoxicity, organelle dysfunction, and vascular dysfunction. Structural changes include glomerular hypertrophy, GBM thickening, and tubular injury. Hyperfiltration leads to tubular hypoxia and fibrosis. EMT contributes to fibrosis through TWIST1, SNAI1, and YAP1. Inflammation and oxidative stress create a vicious cycle, with neutrophil extracellular traps (NETs) exacerbating GEC injury. Lipotoxicity involves lipid accumulation and organelle dysfunction, while mitochondrial dysfunction and vascular changes further impair kidney function. Epigenetic changes, including metabolic memory, also play a role in disease progression. Diagnosis of DKD involves persistent albuminuria, reduced eGFR, and the presence of diabetic retinopathy. The 2012 KDIGO guidelines classify albuminuria into three categories. Screening should begin at DM diagnosis and be repeated annually. Kidney biopsy is rarely used but helps in histological classification. Management of DKD includes glycemic control, lipid management, blood pressure control, and dietary restrictions. Glycemic control is crucial, with HbA1c targets individualized based on CKD severity. SGLT2 inhibitors and metformin are first-line therapies. Lipid management involves statins, ezetimibe, and PCSK-9 inhibitors. Blood pressure control targets <120/80 mmHg for CKD patients. Sodium and protein intake should be restricted to reduce albuminuria and slow CKD progression. Nephrotoxic agents should be used cautiously to avoid further renal damage. Combination therapies targeting multiple pathways may improve outcomes. Emerging therapies, including anti-inflammatory and organelle-targeted treatments, offer promising avenues for DKD management.