This study investigated the protective mechanism of curcumin against ulcerative colitis (UC) by examining its preventive and therapeutic effects on UC in mice, as well as its influence on autophagy and apoptosis mediated by the extracellular signal regulated kinase 1/2 (ERK1/2)-mammalian target of rapamycin (mTOR) pathway. C57BL/6 mice were randomly divided into five groups: normal control, model, and low-, medium-, and high-dose curcumin intervention groups. The normal control group received regular drinking water, while the other groups were fed 3% dextran sulfate sodium (DSS) solution in the first week followed by normal water in the second week to establish the UC model. The intervention groups were administered curcumin at doses of 50, 100, and 200 mg/(kg BW·d) via gavage, whereas the control and model groups received an equal volume of 0.5% carboxymethyl cellulose solution. The observation endpoint was either mouse death or day 14 after the first treatment, at which point biological samples were collected for analysis. The results showed that, the model group exhibited significantly reduced survival rate, body weight, colorectal length, B-cell lymphoma-2 (BCL-2) expression, microtubule-associated protein light chain 3 isoform II/I (LC3II/I) ratio, and Beclin 1 levels (P < 0.05) as compared with control group, while disease activity index (DAI), spleen index, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, cysteine aspartate-specific protease 3 (Caspase-3), BCL-2-associated X protein (BAX), p62, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated mTOR (p-mTOR) levels were significantly elevated (P < 0.05). Pathological examination revealed severe inflammatory responses in the colon tissue of the model group. Compared with the model group, curcumin intervention significantly suppressed DSS-induced alterations in these indicators (P < 0.05), alleviated UC symptoms, and exhibited a dose-dependent effect.These findings suggest that curcumin may mitigate DSS-induced UC by modulating autophagy and apoptosis through the ERK1/2-mTOR signaling pathway.