Type 1 and type 2 diabetes, along with their accompanying hyperglycemia, are associated with a multitude of comorbidities including the development of diabetic kidney disease. Although the hallmarks of these metabolic disorders have been well characterized in population and animal studies, it is becoming increasingly apparent that diabetes manifests itself differently in men and women. This review summarizes the recent diabetic literature with a focus on known sex differences in clinical and preclinical studies. It explores the physiological differences of glucose handling and the development of diabetes between men and women. This review also uncovers potential mechanisms for these differences, honing in on the vital role that sex hormone signaling plays in the progression of diabetes and renal complications.