Abstract: Objective This study aims to construct an inulin gel-based oral delivery system co-loaded with phycocyanin-tannic acid composite nanoparticles (P-T@Inulin gel), fully characterize its physicochemical properties, and systematically evaluate its therapeutic potential against dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice. Methods PC-TA composite nanoparticles were successfully fabricated via a pH-induced self-assembly strategy. The successful conjugation and molecular interaction between phycocyanin (PC) and tannic acid (TA) were verified by ultraviolet-visible spectroscopy, proton nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The inulin gel matrix was prepared through heat-induced physical gelation. Subsequently, a rotational rheometer was employed to comprehensively evaluate the rheological properties of P-T@Inulin gel, particularly those before and after PC-TA loading. Furthermore, a DSS-induced mouse model of acute UC was established to assess in vivo therapeutic efficacy of P-T@Inulin gel through controlled administration. Results Spectroscopic analyses confirmed the successful formation of PC-TA composite nanoparticles. These nanoparticles exhibited favorable physicochemical profiles: an average particle size of 262.0 nm, a low polydispersity index of 0.084 indicating narrow size distribution, and a Zeta potential of -29.0 ± 0.5 mV. Transmission electron microscopy images revealed a uniform, regular spherical morphology. P-T@Inulin gel demonstrated robust structural stability, excellent self-healing capability, and typical shear-thinning behavior, thereby meeting the critical prerequisites for an ideal oral colon-targeted delivery system. In vivo efficacy studies demonstrated that, compared with the model group, mice treated with high-dose P-T@Inulin gel exhibited significantly mitigated body weight loss, reduced Disease Activity Index scores, restored colon length to near-normal levels, and ameliorated splenomegaly and thymic atrophy. Histopathological examination further revealed marked reductions in inflammatory cell infiltration, mucosal epithelial defects, crypt destruction, and collagen deposition in the colon tissues of the high-dose treatment group, with histological architecture closely resembling that of the control group. Conclusion P-T@Inulin gel effectively alleviates DSS-induced UC symptoms and repairs the impaired intestinal mucosal barrier in mice. This therapeutic effect is synergistically achieved through the anti-inflammatory and antioxidant activities of PC-TA nanoparticles, coupled with the colon-targeted delivery efficiency and prebiotic benefits of the inulin gel matrix. This integrated "nanocomposite-hydrogel delivery" strategy not only offers a promising novel oral formulation approach for UC treatment but also provides valuable experimental insights for the development of multi-functional gastrointestinal therapeutics.