Background <p>Ulcerative colitis (UC) is one of the two major types of inflammatory bowel disease (IBD), characterized by inflammation of the colon and rectum. The colorectal epithelium, which covers the mucosal surface, maintains homeostasis by supporting commensal microorganisms in the outer mucus layer. Most colorectal epithelial cells (CECs) are absorptive colonocytes distributed primarily in the upper portion of the crypts. These CECs constitute the front-line barrier that modulates mucosal immunity and facilitates the transfer of immune molecules into the lumen. In patients with UC, CECs undergo both apoptosis and pyroptosis. Apoptosis is a physiological, programmed, caspase-dependent, and tightly regulated form of cell death that eliminates aged and damaged cells. In contrast, pyroptosis is an inflammatory, caspase-dependent form of lytic cell death that occurs in response to harmful stressors and toxins. Pyroptosis in CECs involves a broad array of signaling and effector molecules, many of which serve as measurable biomarkers with diagnostic, prognostic, and therapeutic potential.</p> Conclusions <p>Dysregulated colorectal microflora significantly contributes to activating the pyroptotic pathway, initiating an inflammasome- and gasdermin-dependent inflammatory cell death process in UC patients. This review discusses the triggers and pathways of pyroptosis in CECs, evaluates recently identified biomarkers, highlights their potential roles in pyroptosis and as therapeutic targets in managing UC, and candidate compounds that have been shown effective UC therapeutics.</p>