Crohn's disease (CD) is a chronic, relapsing inflammatory disease with increasing incidence and prevalence worldwide. In previous years, the accumulation of microarray data has provided us an approach to obtain further insight into CD. In the present study, the microarray data of CD was comprehensively analyzed using multiple bioinformatics methods, and the pathobiological process of the disease was examined. Gene expression data from colon tissues of patients with CD were obtained from the Gene Expression Omnibus database; following which differentially expressed genes were identified between CD and control sample groups. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate which functions and pathways in which the differentially expressed genes enriched. TargetScan and miRDB databases were then used to predict which microRNAs (miRNAs) regulated the differentially expressed genes. As a result, a total of 432 differentially expressed genes, including 229 upregulated and 203 downregulated genes, including matrix metallopeptidase 3 and glutathione S-transferase alpha 1, were identified in CD samples. These differentially expressed genes were significantly involved in regulation of the inflammatory response, innate immune response, cell migration, extracellular matrix organization, Janus kinase/signal transducers and activators of transcription signaling pathway, and cytokine-cytokine receptor interaction. The miRNA-gene network showed that miR-149-3p and miR-4447 regulated the most differentially expressed genes. These findings extend current understanding of the mechanisms underlying CD, and the differentially expressed genes and regulator miRNAs identified may be used as potential biomarkers and therapeutic targets for CD.