Background/Aims: Disorders of brain-gut interaction (DGBIs) are present in adults and children around the world. Down syndrome (DS) is the most common chromosomal condition in humans. While DS has associations with many organic medical conditions, the frequency of DGBIs in children and adolescents with DS has not previously been studied. We assess the rate of DGBIs in children and adolescents 4-18 years of age with DS in the United States using the Rome IV criteria by caregiver report. Methods: This is a cross-sectional national survey study in which caregivers (n = 114) of children with DS completed an online survey about their child’s gastrointestinal symptoms and quality of life (QoL). Results: Using the Rome IV parent-report diagnostic questionnaire, 51.8% of children met symptom-based criteria for at least 1 DGBI. Functional constipation (36.0%) and irritable bowel syndrome (14.9%) were the most common disorders identified. QoL was lower in children with at least 1 disorder as compared to children who did not meet criteria for any disorders (mean QoL = 62.3 vs mean QoL = 72.9, P < 0.001). Almost all children with DS and concomitant autism (87.5%) had at least 1 DGBI. Conclusions DGBIs are common in children with DS and are associated with diminished QoL.