ABSTRACT– Dialysis is the only mode of available palliative therapeutic modality to patient with end stage of renal disease. Diabetes is one of the foremost common causes of chronic renal disease and affecting large number of diabetic patients. By many theory, hypothesis and study are carried to understand the pathogenesis of Diabetic kidney disease or complication of diabetes i.e. diabetic nephropathy (DN) and based on pathophysiology many drugs and molecules are being developed targeting enzymes, intracellular proteins, micro RNA, Receptor, channel etc. Genes (like NFE2L2, HD1, RPD3 etc.) responsible for synthesis of transcription factor, proteins, enzymes and cytokine factors, intracellular antioxidant factor all play vital role in pathophysiology of DN. Targeting multiple genes, which play important role in pathophysiology of DN with nanoparticle loaded with siRNA or drugs or combination will not only reduce multiple drug and medication burden but also mitigate the disease faster and with reversal of pathological changes with safety, if the challenges are met. It is possible to target multiple genes, which play vital role in fibrosis and extracellular matrix expansion which are key features of DN with biodegradable particle. Each drug by unique mechanism specifically targeting protein, enzymes, receptor, channel etc. mitigates the progress of DN and multiple drugs are needed to inhibit the various mechanism. The approach of silencing the multiple genes or delivering drugs inside the cell organelles with biodegradable nanoparticles is novel, versatile and target specific to inhibit the progress of DN and to reverse the pathological changes efficiently as compared to drugs/molecules, if challenges of nanoparticle formulation are met. Based on the research till date and available resource suggest it is possible to target multiple genes or protein or enzymes or signaling molecules using biodegradable and biocompatible nanoparticles (NP) loaded with siRNA and drugs or combination of drug and siRNA.