Bile acids are not only intestinal detergents, but also act as signaling molecules to control bile acid and metabolic homeostasis. By binding to the nuclear receptor farnesoid X receptor (FXR) or the membrane receptor TGR5, bile acids regulate lipid, glucose, and energy metabolism. The removal of bile acids from the enterohepatic cycle by orally administered sequestrants, nonabsorbable resins that complex bile acids in the intestinal lumen, is an effective treatment to reduce plasma cholesterol concentrations in dyslipidemia. In diabetic patients, sequestrants further lower hyperglycemia, and are thus useful in glycemic control. Here, we review the signaling pathways involved in the glucose-regulatory function of bile acids and our current understanding of the mechanisms behind the glucose-lowering effect of bile acid sequestrants.