Crohn’s disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD), driven by complex interactions among genetic, environmental, and microbial factors. This dissertation presents a dual investigation into (1) the cell-type-specific regulatory architecture of the intestinal mucosa in CD, and (2) the cellular adaptations that occur in the ileal pouch of UC patients. In Chapter 2, a single-cell atlas of chromatin accessibility from biopsies of active and inactive CD and healthy controls reveals 557,310 candidate cis-regulatory elements (cCREs). Topic modeling using cCREs reveals regulatory programs that govern cell type-specific and anatomic location specific functions, as well as those associated with inflammatory responses. Immune cell types show the strongest enrichment for CD heritability, but fine-mapped variants also highlight epithelial and stromal cell involvement at specific loci. Chapter 3 focuses on ileal pouches from UC patients, using single-cell RNA-seq and ATAC-seq to uncover partial colonic metaplasia in pouch. Together, these studies illuminate the diverse cellular and epigenetic mechanisms underlying gut tissue architecture, IBD risk and the plasticity of the intestinal epithelium.