Metabolic disorders, such as insulin resistance, affect many people worldwide due to the prevalence of obesity and type 2 diabetes, which are pathologies that impair glycemic metabolism. Glucose is the primary energetic substrate of the body and is essential for cellular function. As the cell membrane is not permeable to glucose molecules, there are two distinct groups of glucose transporters: sodium-glucose-linked transporters (SGLTs) and the glucose transporter (GLUT) family. These transporters facilitate the entry of glucose into the bloodstream or cytoplasm where it functions in the production of adenosine 5 ́-triphosphate (ATP). This nucleotide acts in several cellular mechanisms, such as protein phosphorylation and cellular immune processes. ATP directly and indirectly acts as an agonist for purinergic receptors in high concentrations in the extracellular environment. Composed by P1 and P2 groups, the purinoreceptors cover several cellular mechanisms involving cytokines, tumors, and metabolic signaling pathways. Previous publications have indicated that the purinergic signaling activity in insulin resistance and glucose transporters modulates relevant actions on the deregulations that can affect glycemic homeostasis. Thus, this review focuses on the pharmacological influence of purinergic signaling on the modulation of glucose transporters, aiming for a new way to combat insulin resistance and other metabolic disorders.