The global prevalence of type 2 diabetes mellitus (T2DM) has increased, as well as complications including diabetic retinopathy. Polymorphisms in transcription factor 7-like 2 (TCF7L2) have been associated with T2DM, with the strongest association attributed to the single-nucleotide polymorphism rs7903146. In this review, we searched the current literature to determine whether an association exists between TCF7L2 polymorphisms rs7903146 with diabetic retinopathy. A systematic search was performed of EMBASE, PubMed, and Scopus using the following search terms: diabetic, retinopathy, polymorphism, genetic, transcription factor 7-like 2, TCF7L2. A manual search was also performed. There was no language or study design restriction. Three full articles and one abstract were reviewed. All studies were retrospective case-control studies that compared the frequency of the wild-type CC genotype and genotypes with the risk T allele. None of the studies found a statistically significant odds ratio. While the number of studies examined was small, this review suggests that there is no risk of diabetic retinopathy among individuals with the TCF7L2 polymorphisms rs7903146; however, the polymorphism may play a small role in diabetic retinopathy. Future prospective studies and trials involving diverse ethnicities that adjust for confounding variables are required to understand the association between TCF7L2 polymorphisms and diabetic retinopathy.