In a mouse model of UC induced by dextran sulfate sodium (DSS), we found that prevention with two forms of S. boulardii postbiotics alleviated colitis symptoms triggered by DSS, mitigated colon tissue damage, maintained the distribution of intestinal occludin and ZO-1 proteins, and suppressed the secretion and expression of TNF-α, IL-1β, and IL-6 in serum and colon tissues. Here, TNF is linked to colitis.