Objective: Although lifestyle-related factors have separately been examined in relation to functional gastrointestinal disorders (FGIDs), there is no epidemiological data on the combined association of lifestyle factors with these conditions. We aimed to examine how combinations of several lifestyle factors were associated with functional dyspepsia (FD), its symptoms, and gastroesophageal reflux disease (GERD) in a large group of Iranian adults. Design, Setting, and Subjects: In a cross-sectional study on 3,363 Iranian adults, we calculated the “healthy lifestyle score” for each participant by summing up the binary score given for 5 lifestyle factors, including dietary habits, dietary intakes, psychological distress, smoking, and physical activity. A dish-based 106-item semi-quantitative validated food frequency questionnaire, General Practice Physical Activity Questionnaire, General Health Questionnaire, and other pre-tested questionnaires were used to assess the components of healthy lifestyle score. To assess FGIDs, a validated Persian version of ROME III questionnaire was used. Results: After adjustment for potential confounders, we found that individuals with the highest score of healthy lifestyle had 79 and 74% lower odds of FD (OR: 0.21; 95% CI: 0.05–0.92) and GERD (OR: 0.26; 95% CI: 0.09–0.69), respectively, compared with those with the lowest score. They were also less likely to have early satiation (OR: 0.28; 95% CI: 0.11–0.73), postprandial fullness (OR: 0.22; 95% CI: 0.09–0.50), and epigastric pain (OR: 0.44; 95% CI: 0.21–0.92). In addition to the combined healthy lifestyle score, low levels of psychological distress, a healthy diet, healthy dietary habits, and nonsmoking were separately and protectively associated with FGIDs. Conclusion: We found that adherence to a healthy lifestyle was associated with lower odds of GERD, FD, and its symptoms in this group of Iranian adults, in a dose-response manner. Individual lifestyle-related factors were also associated with these conditions.