In the pre-Columbian societies of the Americas, a wide range of food practices was observed. However, several countries shared certain staple foods, such as the potato, which has held a significant place in the diet since ancient times. It is important to note that potatoes contain glycoalkaloids, a class of alkaloids with potential toxicity risks when consumed in high concentrations by both humans and animals. This study aims to offer guidance on the presence of glycoalkaloids in potatoes and proposes further research into these compounds in archaeological remains that were utilized as food across all American countries. This recommendation stems from the dearth of studies on this subject, particularly in cases where archaeological discoveries include potato starch granules. In this study, various databases were examined to discover historical insights into the potato and to elucidate the primary aspects of glycoalkaloid chemistry associated with this tuber. The findings underscore the crucial role played by the potato in pre-Columbian cultures of the Americas, particularly in the regions situated along the Andes mountain range. Furthermore, the analysis of its nutritional composition unveiled the prevalence of two key glycoalkaloids in the tuber: α-solanine and α-chaconine. In this research, a comprehensive review of the chemical properties, botanical functions, human metabolism, potential health effects, toxicity thresholds, and available analytical techniques for the detection and quantification of toxic compounds was conducted. The significance of identifying these molecules in archaeological contexts was highlighted, as their presence may prompt investigations into prevalent diseases among historical populations.