BackgroundBoth depression and constipation are universal disorders that seriously affect quality of life. But the phenotypic relationship and causality between depression and constipation are still unclear. MethodsWe first assessed phenotypic relationships by logistic regression analysis using large-scale data extracted from the National Health and Nutrition Examination Survey (N = 11,585). We then evaluated causality by bidirectional two-sample mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data (depression: N = 807,553; constipation: N = 377,277). To investigate whether depression severity affects the causal relationship between depression and constipation, we conducted a further MR study on GWAS data of major depression (N = 480,359). ResultsAbout 11.31 % of the participants in the constipation group suffered from depression, which was significantly higher than the normal bowel group (6.09 %). The observational study showed a positive correlation between depression and constipation (OR = 1.968, 95%CI = 1.530–2.532). Besides, the risk of constipation was higher in participants with severe depression (OR = 2.294, 95%CI = 1.538–3.422) than in participants with mild depression (OR = 1.549, 95%CI = 1.242–1.932). Bidirectional MR analysis revealed an obviously causal effect of depression on constipation, but no causal effect of constipation on depression. In addition, the MR analysis also revealed a causal relationship between major depression and constipation. LimitationThe exact mechanism by which depression affects constipation is still unclear. ConclusionThis study reveals a positive correlation between depression and constipation and the causal effect of depression on constipation. Clinicians should keep the risk of constipation in mind when treating patients with depression.