The duodenum is a short portion of the small intestine connecting the rest of the intestine to the stomach. It is about ten inches (25 cm) long, while the entire small intestine measures about 20 feet (6.5 meters). It begins with the duodenal bulb, bordered by the pyloric sphincter that marks the lower end of the stomach, and is connected by the ligament of Treitz to the diaphragm before leading into the next portion of the small intestine, the jejunum.

The duodenum has four distinct parts, the first three forming a "C" shape. It begins with the superior duodenum, which extends from the pyloric sphincter laterally to the right and posteriorly for about two inches (5 cm). The next section, the descending duodenum, is the middle of the "C". The inferior duodenum passes laterally to the left, and the last portion, the ascending duodenum, joins the jejunum at the duodenojejunal flexure.

Though the duodenum is such a tiny fraction of the small intestine, it is the site of most of the breakdown of the food passing through it. The duodenum is lined with Brunner's glands, which secrete an alkaline mucus that supports the intestinal enzymes and aids in the absorption of nutrients. The pancreatic duct, which introduces bile and pancreatic juice into the small intestine, is directly connected to the descending duodenum. Pancreatic juice contains enzymes that help break down food, while bile aids in the digestion and absorption of fats. The duodenum is responsible for secreting hormones that trigger the pancreatic duct to release pancreatic juice and bile.

The duodenum also serves to neutralize the acidity of the chyme that exits the stomach, an intermediate product in the digestive process. Both the Brunner's glands and the pancreatic duct secrete alkaline fluids to temper the acidity of the chyme. In addition, the mucus secreted by the Brunner's glands helps protect the duodenum from the acidity, making the duodenum much less sensitive than the rest of the small intestine to the acidic chyme. Therefore, the duodenum helps protect the rest of the small intestine by neutralizing the chyme to some extent before it passes into the jejunum.