Indigestion can be caused by a condition in the digestive tract called the gastroesophageal reflux disease (GERD), cancer, peptic ulcer disease, and abnormality of the pancreas or bile ducts. If the condition improves or resolves, the symptoms of indigestion usually improve.

Sometimes the causes of indigestion in a person cannot be diagnosed. This type of indigestion, called functional dyspepsia, is thought to occur in the area where the stomach meets the small intestine. The indigestion may be associated to abnormal motility, the squeezing or relaxing action of the stomach muscle as it receives, digests, and moves food into the small intestine.

The main cause of indigestion is usually the stomach acid reflux. Stomach acid helps to digest food and protects human body from infections. Stomach, esophagus and intestine are lined with a mucus layer and this layer acts as a barrier against the stomach acid. The acid irritates tissues underneath when this mucus layer is damaged. For this reason the sphincter connecting the esophagus and stomach does not work properly causing stomach acid reflux.

A bacterium called "Helicobacter pylori" can cause gastritis thus resulting in indigestion. This bacterium lives in the mucus layer of the stomach but very few people have this problem. In a normal human body a muscular sheet called diaphragm separates the lungs and chest from the abdomen and stomach is completely below the diaphragm. But some people have their stomachs sliding up into the chest cavity known as "Hiatus hernia". This "Hiatus hernia" often causes the acute pain and heartburn. Some of the vital factors, which cause indigestion, include, intake of junk food, alcohol, caffeinated beverages and medicines like asliirin and anti-inflammatory medicines. Smoking habits, irregular dieting, stress, anxiety, pregnancy and lielitic ulcer are also considered as cause of indigestion. In taking alcohol, various diseases like ulcer, which hampers the functioning of digestive system and can also, aggravate the problem of indigestion. Eating heavy foods, swallowing of food or quick eating also causes indigestion.