Crohn’s disease (CD) is a chronic and relapsing inflammatory bowel disorder that has been shown to generate neurological impairments, which has the potential to signify disease activity in an underlying neurological manner. The objective of this study was to investigate the abnormalities of brain microstructure and the corresponding functional connectivity (FC) in patients with CD, as well as their associations with disease condition. Twenty-two patients with CD and 22 age-, gender-, and education-matched healthy controls (HCs) were enrolled in this study. All subjects underwent mean apparent propagator (MAP)-MRI and resting-state functional magnetic resonance imaging (MRI) (rs-fMRI) data collection. Each patient was evaluated clinically for the condition and duration of the disease. The MAP metrics were extracted and compared between two groups. Pearson’s correlation analysis was conducted to determine the relationship between disease characteristics and significantly abnormal MAP metrics in the CD group. Regions of interest (ROIs) for ROI-wise FC analysis were selected based on their correlation with MAP metrics. Results showed that multiple brain regions, including the parahippocampus and thalamus, exhibited statistically significant differences in MAP metrics between CD patients and HCs. Additionally, CD patients exhibited decreased FC between the left parahippocampus and bilateral thalamus, as well as the right parahippocampus and bilateral thalamus. The findings of this work provide preliminary evidence that structural abnormalities in the parahippocampal gyrus (PHG) and thalamus, as well as decreased FC between them, may reflect the degree of inflammatory of the disease and serve as brain biomarkers for evaluating CD activity.