Curcumin has been proven to be an effective strategy for reducing inflammatory responses. However, low bioavailability and instability at the physiological pH have limited its anti-inflammatory activity in ulcerative colitis patients. In the present study, a complex of curcumin and konjac glucomannan (KGM) effectively inhibited intestinal inflammation and this effect was associated with KGM degradation degrees. Results demonstrated that treatment with the complex markedly mitigated colitis symptoms and decreased inflammatory cytokines levels, especially in the complex treatment groups with K110 (KGM treated in 110 °C) and konjac oligosaccharides (KOSs). Furthermore, increasing the KOS content in KOC (the complex of curcumin and KOS) promoted the gene expressions of the intestinal barrier and inhibited the gene expressions of inflammatory cytokines, as well as improved gut microbiota dysregulation. Overall, our studies suggest that the complex of curcumin and KGM exerts effective anti-inflammatory effects by regulating the intestinal immune response and modulating microbiota diversity and composition.