Canonical transient receptor potential (TRPC) channel proteins have been identified as downstream molecules in a G protein-coupled receptor signaling pathway and are involved in a variety of cell functions due to their ability to regulate intracellular calcium signaling. TRPC channel physiology has been an increasingly interesting and relevant topic over the last decade, and the outcomes from various studies have advanced our understanding of TRPC function in the normal state. Recently, attention has turned to whether or not TRPC proteins are implicated in diseases. Emerging evidence suggests a significant contribution of several isoforms of TRPC proteins to cardiovascular as well as renal diseases. This review focuses on the implication of TRPC proteins as they pertain to diabetes. We summarize the recent findings by other investigators as well as ourselves and additionally discuss the important role of TRPC proteins in the development of various diabetic complications, such as diabetic nephropathy and diabetic vasculopathy. The underlying mechanisms which contribute to these complications are also outlined. Lastly, we elaborate on the role of TRPC proteins as a potential therapeutic target for treating diabetes-associated diseases.