The aim of this study was to investigate the protective effects and mechanism of curcumin on dextran sulfate sodium (DSS)-induced intestinal fibrosis in mice. Fifty C57BL/6 mice were randomly divided into normal control group, model group, curcumin in low dose group, curcumin in middle dose group, and curcumin in high dose group. The normal control group was fed with normal drinking water. The remaining mice were alternately fed with 2.5% DSS aqueous solution and normal drinking water every week for 6 weeks to establish intestinal fibrosis model. During the modeling process, mice in the curcumin treatment group were orally administered curcumin at doses of 50, 100, and 200 mg/( kg BW·d) , respectively. Mice in the control group and model group were orally administered with an equal volume of 0.5% carboxymethyl cellulose solution. During the experiment, the body weight and disease activity index (DAI) of mice were recorded every week, and the mice were sacrificed after the last curcumin treatment. Colorectal length and spleen weight were measured. The biological indicator of collagen deposition, ferroptosis, and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in colon tissue were detected. Masson staining was performed to observe pathological changes of colon tissue. The results showed: compared with the control group, the body weight, colorectal length, glutathione (GSH) , glutathione peroxidase 4 (GPX4) , solute carrier family 7 member 11 (SLC7A11) , Nrf2, and HO-1 of mice in the model group were significantly decreased (P < 0.05) . DAI, spleen weight, collagen type I alpha 1 (COL1A1), hydroxyproline (Hyp) , lipid peroxide (LPO), ferrous ion (Fe²⁺) , and ferritin heavy chain 1 (FTH1) of mice in the model group were significantly increased (P < 0.05) . Masson staining showed that a large number of collagen fibers appeared in the colon tissue of mice in model group. Compared with the model group, curcumin treatment significantly inhibited DSS-induced changes of various indicators (P < 0.05) ,  and alleviated the degree of intestinal fibrosisin a dose-dependent manner. These results suggested that curcumin inhibited DSS-induced ferroptosis by regulating the Nrf2/HO-1 signaling pathway and further played a protective role on intestinal fibrosis.