BACKGROUND: Inflammatory bowel disease (IBD) and autoimmune disorders result from immune system dysregulation. However, the genetic overlap between them remains unclear. Our study aimed to investigate the genetic mechanisms and structure of IBD from the perspective of autoimmune disorders. METHODS: The genetic correlation (rg) between traits can provide valuable information about the shared underlying biological mechanisms. Utilizing summary statistics from genome-wide association studies, we delved into the genetic correlation, shared inheritance, and potential causality of IBD (N = 34,652) with autoimmune disorders (N = 1,755,610). We performed transcriptomics at the gene level, multi-marker analyses of genome annotations, and enrichment analyses of biological pathways to highlight shared and diverse perspectives. RESULTS: There were significant genetic correlations between IBD and ankylosing spondylitis (rg = 0.327), rheumatoid arthritis (rg = 0.242), type 1 diabetes (rg = - 0.061), psoriasis (rg = 0.246), and ankylosing spondylitis (rg = 0.308). We identified 110 unique regions (including 5p33.3, 10q25.3, and 22q13.31) after a consistent study at the gene levels. By implementing transcriptomics techniques, we discovered potential common biological mechanisms in several tissues, including blood, spleen, thyroid, and pancreas, revealing potential common biological mechanisms involving lincRNA, protein-coding, and pseudogenes. CONCLUSION: Our study demonstrated hypothesized pleiotropic genomic regions that provide important clues to delve into the genetic basis of IBD and autoimmune disorders on the basis of multi-omics. Moreover, we have identified shared pathogenic processes and potential common therapeutic targets among these diseases. Key Points * The finding provides a new perspective on the genetic basis of inflammatory bowel disease and autoimmune disease across multi-omics platforms. * Fine mapping of functional summary-based imputation and causal genomes has identified hypothesized pleiotropic genomic regions. * The identified genes and pathways may offer innovative targets for the prevention of immune-related diseases.