In Brief This article reports on an investigation of whether an intensive lifestyle intervention (ILI) would reduce gastrointestinal symptoms over 4 years of follow-up for participants in the Action for Health in Diabetes (Look AHEAD) trial compared to a diabetes support and education (DSE) group. Look AHEAD is a randomized, multicenter trial comparing overweight and obese adults with type 2 diabetes treated with ILI versus DSE. ILI, and weight loss in general, had beneficial effects on gastrointestinal (GI) symptoms, with some variability in the strength of the effect depending on the specific symptom and time course. Potential modifiers were analyzed, yet ILI retained an association with improvement in GI symptoms.