Abstract: This study constructed an inulin gel oral delivery system loaded with phycocyanin-tannic acid (PC-TA) nanoparticles (PC-TA@Inulin gel), characterized its physicochemical properties, and evaluated its therapeutic effect on dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice. PC-TA nanoparticles were prepared via pH-induced self-assembly, and spectroscopic methods were employed to verify the successful conjugation of PC and TA. The drug-loaded gel was fabricated by physical gelation, and its rheological properties were subsequently analyzed. A DSS-induced UC mouse model was established to evaluate in vivo therapeutic efficacy. The results showed that PC-TA nanoparticles had an average particle size of 262.0 nm, a polydispersity index of 0.084, and a Zeta potential of (–29.0 ± 0.5) mV, presenting a regular spherical structure. PC-TA@Inulin gel possessed favorable structural stability, self-healing capacity and typical shear thinning behavior, which satisfied the requirements for oral colon-targeted delivery. In vivo experiments confirmed that high-dose PC-TA@Inulin gel significantly alleviated body weight loss, reduced the disease activity index, restored colon length, ameliorated splenomegaly and thymic atrophy, and mitigated pathological damages including inflammatory cell infiltration and mucosal defect in the colon tissues of UC mice. In conclusion, this delivery system can effectively relieve UC symptoms in mice and repair the intestinal mucosal barrier through the synergistic anti-inflammatory and antioxidant effects of PC and TA, coupled with the colon-targeted delivery property and prebiotic effect of inulin gel, providing a novel oral formulation strategy and experimental basis for the clinical treatment of UC.