<p>Diabetic nephropathy (DN) is a crucial early microvascular difficulty of diabetes mellitus, remains a leading cause of end-stage renal disease worldwide. DN progresses through multifactorial molecular mechanisms triggered by persistent hyperglycemia, oxidative stress, inflammation, and fibrosis. Although conventional strategies, including the utilization of RAAS and ACE inhibitors, provide symptomatic relief, they often fail to halt disease progression. Therefore, plant-derived bioactive compounds with multi-target potential have come to light as promising alternatives for DN management. The current review critically investigates the molecular mechanisms of DN pathogenesis and focuses on phytoconstituents such as flavonoids, alkaloids, terpenoids, and saponins that potentially target major DN signalling pathways. By bridging existing knowledge gaps and focusing on natural therapies, this review offers a comprehensive understanding of DN progression and explores innovative therapeutic strategies to mitigate its burden. Advancing research through randomized clinical trials and meta-analyses of plant-based treatments may pave the way for more effective and safer approaches to DN management.</p> Graphical Abstract <p>Molecular Insights and plant based treatment for diabetic nephropathy. </p>