In this study, gamma-cyclodextrins (gamma-CD) and epigallocatechin-3-gallate (EGCG) were designed to form an inclusion complex (EGCG-gamma-IC) for ulcerative colitis (UC) treatment. The drug-excipient combined therapeutic potential of gamma-CD and EGCG was verified, when stability and compliance were also achieved. EGCG-gamma-IC effectively inhibited the secretions of NO, TNF-alpha, and IL-6 and the intracellular ROS in RAW264.7 cells. The effectiveness of EGCG-gamma-IC in treating DSS-induced acute UC in mice was observed including improving the histological conditions of the colon, reducing the levels of IL-1beta, IL-6, and TNF-alpha in serum, and restoring MPO, GSH, and sIgA levels in intestinal tissues. Moreover, EGCG-gamma-IC had a more prominent effect on regulating bacterial dysbiosis caused by DSS than EGCG and gamma-CD alone. Therefore, EGCG-gamma-IC designed here displayed UC treating capacity with safety in the long-term application and promised an industrial production potential due to its excellent storage stability.