Background: Considering the high comorbidity, shared risk factors, and genetic pathways between irritable bowel syndrome (IBS) and major depressive disorder (MDD), we hypothesized that there would be both shared and disorder-specific alterations in brain function. Methods: A total of 39 IBS patients, 39 MDD patients, and 40 healthy controls (HCs) were enrolled and matched for sex, age, and educational level. All subjects underwent resting-state functional MRI. The clinical variables of anxiety, depression, gastrointestinal symptoms and alexithymia were recorded. The 12 subregions of the striatum were employed as seeds to assess their functional connectivity (FC) with every voxel throughout the whole brain. Results: Compared to HC, IBS and MDD patients exhibited aberrant frontal-striatal circuitry. We observed a common decrease in FC between the dorsal striatum and regions of the hippocampus, sensorimotor cortex, and prefrontal cortex (PFC) in both IBS and MDD patients. Patients with IBS exhibited disorder-specific decreases in FC within the striatum, along with reduced connectivity between the ventral striatum and sensorimotor cortex. In contrast, MDD patients showed disorder-specific hyperconnectivity in the medial PFC-limbic system. Receiver operating characteristic curve analysis showed that frontal-striatal FC values could serve as transdiagnostic markers of IBS and MDD. Within the IBS group, striatal connectivity was not only negatively associated with weekly abdominal pain days but also negatively correlated with the levels of anxiety and alexithymia. Conclusions: This exploratory analysis indicated that patients with IBS and MDD exhibited both shared and disorder-specific frontal-striatal circuit impairments, potentially explaining both comorbidity and distinct phenotypes.