This comparative cross-sectional study evaluates the prevalence of comorbid depression in patients with Irritable Bowel Syndrome (IBS) and chronic gastritis (CG) at an urban outpatient clinic. A total of 178 patients—89 diagnosed with IBS and 89 with CG—were assessed for depressive symptoms using the Beck Depression Inventory-II (BDI-II) and the 21-item Hamilton Depression Rating Scale (HDRS-21). Our findings indicate a significantly higher prevalence of depression in IBS patients, with 71.9% meeting criteria for depression based on the BDI-II and 70.8% based on the HDRS-21, compared to 10.1% in CG patients. The study highlights that retardation symptoms, including depressed mood and loss of interest, are central to depression and contribute to substantial impairment in daily activities and quality of life. Additionally, anxiety and somatization were prominent in the IBS cohort. This study emphasizes the need for integrated care approaches that address both gastrointestinal and psychological symptoms, fostering improved patient management and outcomes. Our results underscore the importance of regular psychological assessments in IBS patients, particularly those without overt depressive symptoms, to enhance their overall well-being.