BACKGROUND: Anxiety is a common comorbidity in patients with Crohn's disease (CD). Data on the imaging characteristics of brain microstructure and cerebral perfusion in CD with anxiety are limited. AIM: To compare the imaging characteristics of brain microstructure and cerebral perfusion among CD patients with or without anxiety and healthy individuals. METHODS: This prospective comparative study enrolled consecutive patients with active CD and healthy individuals who visited the study hospital between January 2022 and January 2023. Anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety. The imaging characteristics of brain microstructure and cerebral perfusion were measured by diffusion kurtosis imaging and intravoxel incoherent motion. RESULTS: A total of 57 participants were enrolled. Among the patients with active CD, 16 had anxiety. Compared with healthy individuals, patients with active CD demonstrated significantly lower radial kurtosis values in the right cerebellar region 6, lower axial kurtosis (AK) values in the right insula, left superior temporal gyrus, and right thalamus, and higher slow and fast apparent diffusion coefficients (ADC and ADC) in the bilateral frontal lobe, bilateral temporal lobe, and bilateral insular lobe (all < 0.05). Compared with patients with CD without anxiety, patients with CD and anxiety exhibited significantly higher ADC values in the left insular lobe and lower AK values in the right insula and right anterior cuneus (all < 0.05). CONCLUSION: There are variations in brain microstructure and perfusion among CD patients with/without anxiety and healthy individuals, suggesting potential use in assessing anxiety-related changes in active CD.