Background/Aims: Accumulating evidence based on a few studies suggests a relationship between depression and functional constipation. This study examined whether depression is associated with a higher risk of functional constipation and whether it is gender specific. Methods: This cross-sectional study was carried out on 3,362 adults aged 18-55 years. In this study, functional gastrointestinal symptoms were determined using an Iranian reliable and valid version of the modified Rome III questionnaire. The Iranian validated version of the hospital anxiety and depression scale was used to evaluate the psychological health. Scores of eight or more on the depression subscale in the questionnaire were considered the presence of depression. Simple and multiple binary logistic regression were used for data analysis. Results: The mean±SD age of participants was 36.29±7.87 years, and 58.5% were female. The prevalence of depression and constipation in the study sample was 28.6% and 23.9%, respectively. In the full adjusted model, in the total sample, depressed people showed a significantly higher risk of constipation; adjusted OR (AOR), 1.69 (95% CI, 1.37-2.09). Although a significant association was observed between depression and constipation in both genders, the association was stronger in men than women (AOR, 2.28; 95% CI, 1.50, 3.63 vs. AOR, 1.55; 95% CI, 1.21, 1.99). Conclusions These study findings showed that depressed people are at a significantly higher risk of being affected by constipation. The current study findings justify the importance of mental health evaluations in all patients with functional gastrointestinal disorders, particularly among constipated individuals.