Objective: Inflammatory bowel disease (IBD) is associated with elevated levels of anxiety and depression and a reduction in health-related quality of life (HRQoL). Nonadherence to treatment is also frequent in IBD and compromises outcomes. Religious coping plays a role in the adaptation to several chronic diseases. However, the influence of religious coping on IBD-related psychological distress, HRQoL, and treatment adherence remains unknown. Method: This cross-sectional study recruited 147 consecutive patients with either Crohn’s disease or ulcerative colitis. Sociodemographic data, disease-related variables, psychological distress (Hospital Anxiety and Depression Scale), religious coping (Brief RCOPE Scale), HRQoL (WHOQOL-Bref), and adherence (8-item Morisky Medication Adherence Scale) were assessed. Hierarchical multiple regression models were used to evaluate the effects of religious coping on IBD-related psychological distress, treatment adherence, and HRQoL. Results: Positive RCOPE was negatively associated with anxiety (b = 0.256; p = 0.007) as well as with overall, physical, and mental health HRQoL. Religious struggle was significantly associated with depression (b = 0.307; p < 0.001) and self-reported adherence (b = 0.258; p = 0.009). Finally, anxiety symptoms fully mediated the effect of positive religious coping on overall HRQoL. Conclusion: Religious coping is significantly associated with psychological distress, HRQoL, and adherence in IBD.