Objectives: Potatoes are an important staple crop across the world and particularly in the Andes, where they were cultivated as early as 10,000 years ago. Ancient Andean populations that relied upon this high-starch food to survive could possess genetic adaptation(s) to digest potato starch more efficiently. Here, we analyzed genomic data to identify whether this putative adaptation is still present in their modern-day descendants, namely Peruvians of Indigenous American ancestry. Materials and methods: We applied several tests to detect signatures of natural selection in genes associated with starch-digestion, AMY1, AMY2, SI, and MGAM in Peruvians. These were compared to two populations who only recently incorporated potatoes into their diets, Han Chinese and West Africans. Results: Overlapping statistical results identified a regional haplotype in MGAM that is unique to Peruvians. The age of this haplotype was estimated to be around 9547 years old. Discussion: The MGAM haplotype in Peruvians lies within a region of high transcriptional activity associated with the REST protein. The timing of this haplotype suggests that it arose in response to increased potato cultivation and attendant consumption. For Peruvian populations that relied upon the high-starch potato as a major source of nutrition, natural selection likely favored these MGAM variant(s) that led to more efficient digestion and increased glucose production. This research provides further support that detecting subtle shifts in human diet can be a major driver of human evolutionary change, as these results indicate that there is global variation in human ability to better digest high-starch foods.