The aim of this study was to investigate the topological reorganization of the brain default mode network (DMN) in patients with irritable bowel syndrome (IBS) using resting-state functional magnetic resonance imaging (rs-fMRI). With approval by our ethics committee, rs-fMRI was prospectively performed in 31 IBS patients (25 male, 27 ± 8 years) and 32 healthy controls (25 male, 29 ± 9 years). The DMN was determined by unbiased seed-based functional connectivity (FC) analysis and then parcellated into several subregions. FC across all pairs of DMN subregions was computed to construct the DMN architecture, for which topological properties were characterized by graph theoretical approaches. Pearson correlation was performed between abnormal DMN inter-regional FC and network measures and clinical indices in IBS patients. Compared to healthy controls, IBS patients showed decreased DMN inter-regional FC between the anterior cingulate cortex and precuneus, the medial orbital of the superior frontal gyrus (ORBsupmed) and precuneus, and the middle temporal gyrus and precuneus. IBS patients also showed decreased DMN global efficiency (E glob). Inclusion of anxiety and depression as covariates abolished FC between ORBsupmed and precuneus and some E glob differences. The average DMN FC was positively correlated with average E glob (r = 0.47, P = 0.008) and negatively correlated with symptom severity score (r = −0.37, P = 0.04) in IBS patients. In conclusion, IBS patients showed topological reorganization of the DMN to a non-optimized regularity configuration, which may partly be ascribed to high levels of anxiety and depression.