Astaxanthin (Ax) with a strong antioxidant activity is beneficial to human health, but its application is limited by its highly unsaturated structure and poor water-solubility. Ax-enriched colon targeted alginate particles (Ax-Alg) was prepared by high-pressure spraying and ionic gelation, and most of particles was in the range of 0.5–3.2 μm in a diameter. The in vitro models showed that Ax-Alg can maintain the structural integrity in the different conditions (pH, heat and ion). In addition, Ax-Alg can well tolerate the conditions in the mouth, stomach and small intestine and reach the colon where Ax was released due to fermentation of gut microbiota. Mice experiment showed that Ax-Alg reduced dextran sulfate sodium-induced colitis, involving weight loss, disease activity index, colonic mucosal integrity and inflammation, and oxidative damage. On the other hand, Ax-Alg regulated the gut microbiota composition and reduced the abundances of Bacteroidetes members that had positive correlation with ulcerative colitis. Ax-Alg had better effect on the treatment of ulcerative colitis than oil-in-water emulsion, which can be attributed to the synergistic effect of Ax and alginate. This study can be helpful for the application of colon-targeted delivery system in the foods and treatment of colon diseases. • Fabrication of astaxanthin-enriched colon-targeted alginate particle. • Alginate particle can maintain stability with pH, ion and temperature variations. • Alginate particle can tolerate the conditions of the human upper digestive tract. • Astaxanthin is released in the colon due to fermentation of gut microbiota. • Astaxanthin-alginate particle had better effect due to their synergistic action. [ABSTRACT FROM AUTHOR]