Curcumin and resveratrol are two natural products, which have been described as potential anti‑inflammatory, anti‑tumor, and anti‑oxidant molecules. The aims of the present study were to investigate the protective effect of curcumin and resveratrol on dextran sulfate sodium (DSS)‑induced ulcerative colitis (UC) in mice, in addition to understanding the underlying molecular mechanisms. In order to accomplish this, BALB/c mice received drinking water containing 3.5% DSS. Curcumin (50 mg/kg/day) or resveratrol (80 mg/kg/day) were administered orally for 7 days. Survival rate, body weight, disease activity index score, colon length, pro‑inflammatory cytokines, and the expression autophagy‑associated proteins, and mechanistic target of rapamycin (mTOR) and sirtuin 1 (SIRT1) were measured. Curcumin or resveratrol treatment prolonged the survival of mice with UC, reduced body weight loss and attenuated the severity of the disease compared with the DSS‑treated mice. This effect was associated with a substantial clinical amelioration of the disruption of the colonic architecture and a significant reduction in pro‑inflammatory cytokine production. Furthermore, curcumin or resveratrol significantly downregulated the expression of autophagy‑related 12, Beclin‑1 and microtubule‑associated protein light chain 3 II, and upregulated the expression of phosphorylated mTOR and SIRT1 in the colon tissue, compared with those in the DSS‑treated group. These results suggest that curcumin and resveratrol exert protective effects on DSS‑induced UC, partially through suppressing the intestinal inflammatory cascade reaction, reducing autophagy and regulating SIRT1/mTOR signaling.