Diabetic kidney disease (DKD) is a significant cause of chronic kidney disease (CKD) and increases the risk of cardiovascular incidents. The pathogenesis of DKD involves hemodynamic, inflammatory, and metabolic factors, leading to fibrosis. Genetic predisposition and unhealthy lifestyle practices contribute to its development and progression. Despite recent advancements in therapies, including angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptor antagonists (NS-MRAs), current treatments still fail to effectively arrest DKD progression. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) show promise as renal protectors, potentially slowing DKD progression. Other agents like pentoxifylline (PTF), selonsertib, and baricitinib also hold potential due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, including lifestyle modifications and drug therapy, can effectively decelerate DKD progression. Combining multiple drugs, as recommended for heart failure treatment, may be more effective than single-drug therapy. Understanding the underlying mechanisms, such as inflammatory and fibrotic factors, is crucial for optimizing DKD management. Long noncoding RNAs (lncRNAs) are emerging as important biomarkers and therapeutic targets. The review discusses the current understanding of DKD pathogenesis, potential mechanisms, and the latest evidence-based interventions, highlighting the need for more effective treatments to manage and potentially reverse DKD.Diabetic kidney disease (DKD) is a significant cause of chronic kidney disease (CKD) and increases the risk of cardiovascular incidents. The pathogenesis of DKD involves hemodynamic, inflammatory, and metabolic factors, leading to fibrosis. Genetic predisposition and unhealthy lifestyle practices contribute to its development and progression. Despite recent advancements in therapies, including angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptor antagonists (NS-MRAs), current treatments still fail to effectively arrest DKD progression. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) show promise as renal protectors, potentially slowing DKD progression. Other agents like pentoxifylline (PTF), selonsertib, and baricitinib also hold potential due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, including lifestyle modifications and drug therapy, can effectively decelerate DKD progression. Combining multiple drugs, as recommended for heart failure treatment, may be more effective than single-drug therapy. Understanding the underlying mechanisms, such as inflammatory and fibrotic factors, is crucial for optimizing DKD management. Long noncoding RNAs (lncRNAs) are emerging as important biomarkers and therapeutic targets. The review discusses the current understanding of DKD pathogenesis, potential mechanisms, and the latest evidence-based interventions, highlighting the need for more effective treatments to manage and potentially reverse DKD.