Abstract: High-altitude regions, characterized by their elevated altitude, are subject to a complex set of environmental conditions including intense ultraviolet radiation, low oxygen levels, low temperatures, and low humidity. These distinctive environmental features lead to unique dietary patterns, lifestyles, and physiological adaptations. Notably, individuals who have just moved into high-altitude areas and those who live there on a long-term basis undergo specific adaptive adjustments in glucose metabolism. Typically, newcomers experience transient elevations in blood glucose levels, which gradually decline after prolonged residence at high altitudes to levels even lower than those found at low altitudes. In general, current findings of observational studies generally suggest a decreased risk of diabetes mellitus among populations inhabiting high-altitude regions. However, the glucose metabolism varies among populations from different high-altitude regions across the world, which indicates that the reshaping of glucose metabolism induced by high altitudes is a complicated phenomenon. This article provides an overview of the impact of various components of high-altitude environment, characteristic lifestyle factors, and socioeconomic development levels on glucose metabolism and the related diseases and the potential mechanisms involved. The aim is to offer valuable insights for researchers investigating glucose metabolism in high-altitude settings.