Inflammatory bowel disease (IBD) is a group of chronic relapsing diseases associated with inflammatory disorders and microbial dysbiosis of the intestine. The use of traditional Chinese medicine (TCM) to treat colitis has the advantage of fewer side effects, but the molecular mechanism is not clear. Recently, miRNAs have been recognized as novel functional small molecules in plants that have regulatory effects on biological activities. This study mainly investigated the mechanism of action of MIR2911 from Honeysuckle, the main component of TCM preparations for colitis. The results demonstrated that MIR2911 can be absorbed through the diet and secreted within host small extracellular vesicles (sEVs), acting directly on intestinal bacteria, reducing the abundance of Escherichia-Shigella, and improving colitis symptoms. This study provides a new theoretical basis for the molecular mechanism of TCM therapy and identifies a potential new drug a new drug target for the treatment of colitis.