Digestive activity regulation hinges on three primary components. Activation is prompted by a multitude of mechanical and chemical indicators, primarily detected by receptors within the stomach and intestines' walls. These receptors predominantly respond to factors such as mechanical stretching of the organ walls, changes in pH and osmolarity, and the presence of digesting materials and their by-products.

The effectors in this regulation system are glands and smooth muscles. Activation of these elements results in reflexes that stir the muscle layers of the digestive tract, facilitating the thorough mixing and transit of contents along the tract. Additionally, glands can also be stimulated or suppressed to alter the secretion of digestive enzymes into the organ lumen or hormones into the bloodstream.

Neuronal and hormonal controls, both intrinsic and extrinsic, are also involved in governing digestive activity. Short reflexes are managed by intrinsic nerves within the enteric nervous system, whereas extrinsic nerves control long reflexes. Hormone-producing cells are found in the stomach and small intestine. They release their products into the interstitial fluid of the extracellular space when stimulated. These hormones are then transported via the bloodstream and interstitial fluid to their target cells in the same or different organs of the digestive tract, where they affect secretion or contraction processes.

Numerous hormones participate in the digestion process. Gastrin, the stomach's main hormone, is released when food enters the stomach, prompting the parietal cells of the stomach lining to produce gastric acid. Other hormones impacting the gastrointestinal system are created and influence the gut and its associated organs. The duodenum generates hormones such as secretin, which triggers the pancreas to produce a bicarbonate-rich watery secretion. Another hormone, cholecystokinin (CCK), encourages the pancreas to release digestive enzymes, stimulates bile production in the liver, and promotes bile release from the gallbladder. Additionally, gastric inhibitory peptide, also known as glucose-dependent insulinotropic peptide (GIP), primarily stimulates insulin secretion in response to glucose intake. GIP slows down gastric secretion, emptying, and motility. These hormones are produced by special epithelial cells called enteroendocrine cells that are found in the mucosal lining of the stomach and small intestine. Once produced, these hormones enter the bloodstream, enabling them to reach the organs they target.

Furthermore, local environmental factors, such as pH, volume, or chemical composition of the intestinal contents, can have a direct effect on the digestive activity within a specific segment of the digestive tract. For example, the stretching of the intestinal wall can trigger localized muscle contractions. In certain circumstances, local factors can prompt the release of chemicals. Molecules such as prostaglandins and histamine, released into the interstitial fluid, can affect the neighboring cells within a localized tract area. Digestive hormones may also alter the sensitivity of smooth muscle cells to neural signals, either increasing or decreasing it. These hormones are produced by enteroendocrine cells in the digestive tract and reach their target organs via the bloodstream.