Diabetic kidney disease (DKD) poses a major global health challenge, affecting millions of individuals and contributing to substantial morbidity and mortality. Traditional treatments have focused primarily on managing symptoms and slowing disease progression rather than reversing or halting kidney damage. However, recent advancements in natural compound research have unveiled promising new avenues for therapeutic development. Extensive research has been conducted to showcase the antioxidant advantages for kidney health, supporting the potential effectiveness of natural and synthetic products in clinical and experimental research. Bioactive substances found in large quantities in food, such as polyphenols, have emerged as adjuvants. This review manuscript aims to provide a comprehensive overview of natural compounds and their potential efficacy, mechanisms of action, and clinical applications in the prevention and treatment of various kidney diseases. This review emphasizes the connection between oxidative stress and inflammation in diabetic nephropathy (DN), which leads to harmful effects on kidney cells due to pathological damage. A lower incidence of DM2-related problems and a slower progression of end-stage renal disease have been associated with the consumption of these compounds.