Butyrate has recently emerged as a promising substance for the therapy of colitis. To overcome the shortcomings implicated in the existing delivery systems of butyrate, we utilized butyrylated starch to specifically deliver butyrate to the colon. Herein, we describe the stable loading of butyrate via chemical bonds with a heterogeneous distribution throughout the particle. Butyrylated starch supply increased butyrate as well as total short-chain fatty acid contents at the end of the intervention period. Moreover, butyrylated starch showed multiple effects on the suppression of DSS-induced colitis. From the observation of the gut–liver axis, reduced hepatic inflammation and hepatocyte damage further confirmed alleviated colonic inflammation. Given that butyrylated starch has the combined effects of specific release of butyrate in the colon and extra supply of fermentable substrates for gut microbiota, this work provides an effective strategy for the assistant therapy of colitis.