The popularity of high-protein diets has surged recently as obesity has become more and more common in the United States and other developed nations. In view of the high prevalence of type 2 diabetes and chronic kidney disease among obese people, it is important to understand potential effects of high-protein diets on the kidney. The hypothesis that high-protein diets are nephrotoxic because of their excessive dietary advanced glycation end product (AGE) content and an increased amino acid load that enhances AGE formation in situ was explored. This review discusses the following evidence: (1) High-protein diets are deleterious to the kidney; (2) AGE are metabolic mediators of kidney damage; (3) dietary protein-derived AGE contribute to proinflammatory and pro-oxidative processes in diabetes and kidney disease; and (4) dietary protein-derived AGE produce functional and structural abnormalities that are involved in kidney damage. Future research should consider dietary AGE as a potential therapeutic target for kidney disease in obesity, diabetes, and perhaps other causes of chronic kidney disease.