Intervening in the microbial environment holds promise for enhancing antitumor efficacy by reshaping the tumor microenvironment, yet few strategies have been reported. In a study led by Zou and coworkers, oral hydrogels are introduced to regulate the microbiota balance in the intestines and tumors, triggering an antitumor immune response. This work presents a microbiota-targeted drug delivery system that demonstrates notable efficacy in colon targeting and colon retention for the treatment of colorectal cancer. This represents a significant clinical advancement in treating colorectal cancer, which is particularly vulnerable to microbial infiltration.