5-O-Methylvisammioside (MeV) is a natural compound with putative antioxidant properties, but its anti-colitic mechanisms are unclear.<h4>Purpose</h4>To determine whether MeV alleviates colitis by activating the Nrf2/HO-1 axis and constraining ferroptosis.<h4>Methods</h4>Acute colitis was induced in male Sprague-Dawley rats using dextran sulfate sodium and animals were randomized to vehicle, DSS alone, two MeV doses, or mesalazine as a benchmark control. Here, HMOX1 is linked to colitis.