Heat stress is one of the main threats to dairy cow production; in order to resist heat stress, the animal exhibits a variety of physiological and hormonal responses driven by complex molecular mechanisms. Heat-stressed cows have high insulin activity, decreased non-esterified fatty acids, and increased glucose disposal. Glucose, as one of the important biochemical components of the energetic metabolism, is affected at multiple levels by the reciprocal changes in hormonal secretion and adipose metabolism under the influence of heat stress in dairy cattle. Therefore, alterations in glucose metabolism have negative consequences for the animal’s health, production, and reproduction under heat stress. Lactose is a major sugar of milk which is affected by the reshuffle of the whole-body energetic metabolism during heat stress, contributing towards milk production losses. Glucose homeostasis is maintained in the body by one of the glucose transporters’ family called facilitative glucose transporters (GLUTs encoded by SLC2A genes). Besides the glucose level, the GLUTs expression level is also significantly changed under the influence of heat stress. This review aims to describe the effect of heat stress on systemic glucose metabolism, facilitative glucose transporters, and its consequences on health and milk production.