Guaifenesin (gwi fen' ə sin) (INN) or guaiphenesin (former BAN) is an expectorant drug usually taken orally to assist the expectoration ("bringing up") of phlegm from the airways in acute respiratory tract infections. Guaifenesin works by drawing water into the bronchi. The water both thins mucus and lubricates the airway, facilitating the removal of mucus by coughing. It is sold under several brand names such as Guailife, Humibid, Mucinex, and Robitussin, and it also is included in many over-the-counter cough and cold remedies.

Guaifenesin's molecular formula is C₁₀H₁₄O₄, and its chemical name is 3-(2-methoxyphenoxy)-1,2-propanediol. Its CAS number is 93-14-1. It was first approved by the Food and Drug Administration (FDA) in 1952.

Guaifenesin is also used in the experimental guaifenesin protocol in the treatment of fibromyalgia.