Plant polysaccharides have been reported to possess multiple pharmacological effects that can inhibit the progression of inflammatory diseases. The shell of Camellia oleifera fruits is a byproduct of the C. oleifera industry that is insufficiently utilized. Herein, a novel polysaccharide (CFP-A) was purified from C. oleifera fruit shells, and its structure elucidation and anti-inflammatory activity against dextran sulfate sodium (DSS)-induced ulcerative colitis were investigated. Structural analysis revealed that CFP-A is a neutral heteropolysaccharide with a molecular weight of 5643 Da, primarily comprising arabinose (Ara), galactose (Gal), and glucose (Glc). The main chain of CFP-A was -->3,6)-alpha-d-Galp-(1-->3,6)-alpha-d-Galp-(1-->3,6)-alpha-d-Galp-(1-->3)-alpha-d-Galp-(1-->. The branch chains alpha-d-Galp-(1-->6)-alpha-d-Galp-(1-->, alpha-l-Araf-(1-->[5)-alpha-l-Araf-(1](7)-->3,5)-alpha-l-Araf-(1-->, and alpha-l-Araf-(1-->[4)-alpha-d-Glcp-(1](2)--> were respectively connected at the C6 position of -->3,6)-alpha-d-Galp-(1-->. CFP-A reduced the expression levels of interleukin-6 and interleukin-1beta and the production of nitric oxide in lipopolysaccharide-induced Raw264.7 macrophages; it also downregulated inflammatory factor levels in the colon and alleviated splenic hypertrophy, colonic tissue damage, and apoptosis in DSS-induced colitis. Mechanistically, CFP-A attenuated DSS-induced colonic inflammation in mice by activating the Keap1/Nrf2/HO-1 pathway. Collectively, these findings highlight the potential of CPF-A as a complementary therapy for ulcerative colitis.