BACKGROUND: Abnormalities of neostriatum have been reported to be implicated in Crohn's disease (CD). However, there are few systematic explorations. We aim to explore the changes that occur in the structure and function of the neostriatum and whether these changes are related to the clinical characteristics of CD. METHODS: In this cross-sectional and prospective study, we enrolled 34 CD patients and 31 healthy controls (HCs) for analysis. We performed voxel-based morphometry (VBM) and seed-based functional connectivity (FC) to evaluate the structural and functional changes in the neostriatum. Correlation analysis was used to evaluate the possible relationships between clinical characteristics and neuroimaging findings. RESULTS: CD patients had significantly increased gray matter volume (GMV) in the bilateral putamen compared with HCs. The results showed that CD patients had significantly decreased FC related to the putamen-calcarine cortex, putamen-fusiform gyrus, putamen-inferior temporal cortex (ITC), putamen-parahippocampus, and increased FC associated with the putamen-cuneus/precuneus. Moreover, CD patients showed a positive correlation between the GMV in the left putamen and illness duration (r=0.42, P=0.013). CONCLUSIONS: Our study indicated that CD patients had increased GMV and abnormal FC related to the putamen. The structural and functional differences could reflect that neostriatum may be linked with alterations of aberrant patterns of the default mode network (DMN) and visual processing area.