O/W Pickering emulsion stabilized by acid-modified attapulgite particle was used as template， sesamin was used as core material， and soy protein and chitosan hydrochloride were used as wall material. The preparation process of sesamin-colon targeted microcapsule was optimized through single factor experiment and response surface test. The properties of colon-targeting and sustained-release of microcapsules were investigated through in vitro simulated digestion experiments. Results showed that the optimal preparation process of Pickering lotion was pH 6.0， mass fraction of particle 1.5%， and volume fraction of oil phase 2.0%. The optimal preparation process of sesamin microcapsules was pH 5.0， ratio of core to wall 1∶2.0， ratio of wall material 1∶1.0， temperature of water bath 55 ℃， and time of water bath 3 hours. The encapsulation efficiency of sesamin in microcapsules was (71.36 ± 0.61)%. Sesamin microcapsules had the significant properties of colon-targeting and sustained release. This study provides experimental evidence for the development of sesamin microcapsules as functional foods to improve gut microbiota.