Derangement of glucose metabolism is a key feature of T2DM, with the liver and pancreatic β-cells playing a key role in glucose homeostasis. In the postprandial state, glucose is transported into hepatocytes and either metabolized to fatty acids or CO2, or stored as glycogen. Glucose also acts as a key signal in pancreatic β-cells for regulating insulin secretion. Because GLUT2 and GK expressed in liver and β-cells are responsible for sensing glucose levels in the blood, studies on the regulation of these biomolecules are important in understanding glucose homeostasis in vivo. These molecules are known to be regulated either transcriptionally or post-transcriptionally, and recent studies on the structure and function of promoters of these genes have revealed the involvement of various transcriptional factors in their regulation. Here, we review recent progress in elucidating the transcriptional regulation of glucose sensors in the liver and pancreatic β-cells and the relevance to T2DM.