Linaclotide, (sold under the brand name Linzess in the US and Mexico, and as Constella elsewhere) is a drug used to treat irritable bowel syndrome with constipation and chronic constipation with no known cause. It has a black box warning about the risk of serious dehydration in children in the US; the most common adverse effects in others include diarrhea.

It is an oligopeptide agonist of guanylate cyclase 2C and remains in the GI tract after it is taken by mouth. It was approved in the US and the European Union in 2012.

It is marketed by Abbvie (formerly Allergan) in the United States and by Astellas in Asia;^{[citation needed]} Ironwood Pharmaceuticals was the originator.^{[failed verification]} In 2023, it was the 178th most commonly prescribed medication in the United States, with more than 2 million prescriptions.

Linaclotide is indicated to treat irritable bowel syndrome with constipation and chronic constipation with no known cause.

In June 2023, the indication was expanded in the US to include the treatment of functional constipation.

The US label has a black box warning to not use linaclotide in children less than six years old and to avoid in people from 6 to 18 years old, due to the risk of serious dehydration.

More than 10% of people taking linaclotide have diarrhea. Between 1% and 10% of people have decreased appetite, dehydration, low potassium, dizziness when standing up too quickly, nausea, vomiting, urgent need to defecate, fecal incontinence, and bleeding in the colon, rectum, and anus.

It has not been tested in pregnant women and it is unknown if it is excreted in breast milk.