While a small amount of fat digestion may occur in the mouth via the action of lingual lipase, the majority of lipid digestions begins in the duodenum. The presence of fat in the small intestine triggers release of pancreatic lipase, which enters the duodenum via the pancreatic duct. Fat digestion does not occur in the stomach.

Normal transit time of food through the small intestine is three to eight hours. This is significantly longer than transit time through the stomach due to the wider variety of digestive processes that occur in the small intestine, including the catabolism of proteins, lipids, nucleic acids, and simple and complex carbohydrates.

The two main forms of digestion and chemical and mechanical. Mechanical digestion involves the physical crushing, mixing, and breaking down of food particles into small pieces or slurries. Mechanical digestion primarily occurs with mastication and is carried out to some degree by peristaltic contractions of the stomach and intestine. Chemical digestion is the further breakdown of food particles into their molecular parts. This is carried out primarily via enzymes, HCl, and bile.

The main artery supplying blood to the small intestine is the superior mesenteric artery. This vessel branches off the abdominal aorta and supplies the lower part of the duodenum, the ileum, the jejunum, and two-thirds of the transverse colon. The rest of the colon and the rectum are supplied by the inferior mesenteric artery, while the right hepatic and left gastric supply the liver and stomach, respectively.

Intrinsic factor, a molecule necessary for the absorption of dietary B12, is produced by the parietal cells of the stomach. Its release stimulated by the same factors that stimulate release of hydrochloric acid: histamine, gastrin, and acetylcholine.

Gastric chief cells secrete pepsinogen and chymosin, while beta islet cells of the pancreas secrete insulin. Brunner's glands secrete a mucus that protects th lining of the intestine.

The hydrolysis of oligosaccharides into disaccharides occurs in the duodenum, after the addition of pancreatic amylase from the pancreatic duct.

The muscular sphincter that keeps stomach contents from regurgitating into the esophagus is the lower esophageal sphincter. The upper esophageal sphincter separates the esophagus from the pharynx, the pyloric sphincter separates the stomach from the small intestine, and the ileocecal valve separates the small intestine from the large intestine.

Ghrelin is a hormone produced primarily in the stomach and small intestine. It is secreted when the stomach is empty, triggering a feeling of hunger. When the stomach is stretched, secretion of ghrelin is inhibited. Leptin is a hormone secreted by adipose cells to signal satiety. Gastrin triggers the secretion of stomach acid during digestion, and cholecystokinin (CKK) is a hormone with various roles in the process of digestion, primarily acting as a hunger suppressant and a trigger for the release of digestive enzymes and bile.

The ileocecal sphincter/valve separates the small intestine from the large intestine. The lower esophageal sphincter, also known as the cardiac sphincter, separates the esophagus from the stomach, while the pyloric sphincter separates the stomach from the small intestine.

The system of coordinated peristaltic waves that slowly sweeps food through the small intestine for digestion is called the migrating motor complex. Disorderly motion of this complex can result in a wide variety of gastrointestinal complaints such as vomiting, dumping syndrome, bloating, or indigestion. Segmentation contractions mix the contents of the colon for more absorption, while mass movements serve to propel feces towards the rectum.