Glucose is the primary energy substrate and an essential precursor for cellular metabolism. Maintaining glucose homeostasis necessitates the presence of glucose transporters, as the hydrophilic nature of glucose prevents its passage across the cell membrane. The GLUT family is a crucial group of glucose transporters that facilitate glucose diffusion along the transmembrane glucose concentration gradient. Dysfunction in GLUTs is associated with diseases, such as GLUT1 deficiency syndrome, Fanconi-Bickel syndrome, and type 2 diabetes. Furthermore, elevated expression of GLUTs fuels aerobic glycolysis, known as the Warburg effect, in various types of cancers, making GLUT isoforms possible targets for antineoplastic therapies. To date, 30 GLUT and homolog structures have been released on the Protein Data Bank (PDB), showcasing multiple conformational and ligand-binding states. These structures elucidate the molecular mechanisms underlying substrate recognition, the alternating access cycle, and transport inhibition. Here, we summarize the current knowledge of human GLUTs and their role in cancer, highlighting recent advances in the structural characterization of GLUTs. We also compare the inhibition mechanisms of exofacial and endofacial GLUT inhibitors, providing insights into the design and optimization of GLUT inhibitors for therapeutic applications.