Acculturation to the United States has been previously studied in Spanish-speaking populations, but little is known about the potential relationship between acculturation and type 2 diabetes mellitus (T2DM). The purpose of this review was to explore the relationship between acculturation and T2DM in Spanish-speaking populations in the United States. Selected studies collected from a review of literature were analyzed by population, ethnicity, acculturation scale, and significance. Thirty-two eligible articles showed conflicting data between the effects of acculturation on T2DM. Overall, studies yielded inconclusive results on the significance of the relationship between acculturation and diabetes in Spanish-speaking populations, which merit further investigation.