Gastrointestinal (GI) physiology describes the normal functions of the digestive tract, particularly that of its hollow organs. Within the oropharynx, oesophagus, stomach, small bowel, colon, and rectum, nutrient solids and fluids are ingested, propelled, mixed, digested, and absorbed while non-absorbable materials are stored and excreted. Critical to the digestive process are the exocrine secretions of the pancreas, liver, and gastrointestinal mucosae. These secretions break and dissolve the large, complex, ingested molecules of food into smaller compounds, which are then ready for absorption into the intestinal epithelium and its circulation. The gastrointestinal wall embedding transporters and mucosal enzymes critically controls the absorption of nutrition and exogenous substances, such as drugs, across GI mucosa. The chapter gives an overview of the three major physiological functions of the gastrointestinal system, i.e., are motility, secretion, and digestion/absorption, influencing the fate of nutrition and pharmaceuticals administered into the GI tract.