Inflammatory bowel disease (IBD) is a known medical burden in most developed countries and a significant cause of morbidity. The IBD label includes Crohn's disease (CD) and ulcerative colitis (UC). Pharmacological and surgical intervention are the two main management approaches for IBD. Some drugs have been developed for IBD therapy, but accessibility is limited due to high costs. Furthermore, these agents have demonstrated inactivity over long-term treatment courses. Therefore, an urgent need is present for new treatment options that are safe, able to sustain clinical remission, and improve mucosal gut healing. Seaweed has received much attention in the pharmacological field owing to its various biomedical properties, including the prolongation of blood clotting time, as well as antitumor, anti-inflammation, and antioxidant effects. This study therefore aimed to examine the effects of a dietary polysaccharide-rich extract obtained from Eucheuma cottonii (EC) on a model of colitis. Colitis was induced in male BALB/c mice by the administration of 2.5% (w/v) dextran sulfate sodium (DSS) for 7 days. DSS-induced mice were treated with either one of three different doses of EC extracts (0.35, 0.70, and 1.75 g/kg body weight) or curcumin as a positive control (0.10 g/kg). Mice were sacrificed post-treatment and blood samples were collected. The disease activity index (DAI) and inflammatory cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10) were measured. After treatment for 7 days, EC extract administration protected against weight loss and decreased the colon weight per length ratio. EC extract administration also decreased pro-inflammatory cytokine expression, increased IL-10 levels, and reduced colonic damage. Therefore, a dietary polysaccharide-rich extract from E. cottonii reduced DSS-induced bowel inflammation, thereby becoming a promising candidate for the treatment of colitis.