Calcium participates in most of the biological processes in the human body. The calcium sensing receptor (CaSR), as an important regulator of calcium homeostasis, is expressed in all of the organs of the digestive system. CaSR plays a key role in gastrointestinal physiological function and in the occurrence of digestive disease. For example, the inactivation or mutation of the CaSR gene usually leads to one of several disorders of calcium metabolism. High dietary Ca2+ may stimulate CaSR activation and could both inhibit tumor development and increase the chemotherapeutic sensitivity of cancer cells in colon cancer tissues. Further, CaSR has also been reported to have a potential role in the treatment for diarrheal diseases and the form of pancreatitis that is associated with carbonate stones. Therefore, CaSR is an important target for treating digestive diseases, and the calcimimetics (CaSR agonist) have been confirmed as practical, feasible and effective clinical therapies for hyperparathyroidism. This review intends to explore the role of CaSR in digestive physiology and pathophysiology as well as current treatments utilizing CaSR‑based therapeutics.