Ulcerative colitis (UC) is a gastrointestinal disease. The link between gut microbiota and the inflammatory response in the gut has been recently established. Restoration of gut microbiota suppresses inflammatory signaling. Kuijieling (KJL) decoction, an experimental Chinese medicine formula could ameliorate the symptom of colitis. However, the involvement of gut microbiota in its curative effect remains known. Here, we would like to assess the therapeutic effect of KJL in DSS-induced UC model. Mouse feces were collected, followed by 16S rRNA sequencing. Kuijieling decoction improved gut microbial homeostasis and suppressed inflammation in the UC model. A 5-fold cross-validation and random forest analysis identified seven signature bacterial taxa representing the DSS-mediated pathogenic condition and recovery stage upon KJL decoction treatment. Overall, the findings support the notion of KJL decoction-mediated restoration of gut microbiota as a critical step of inducing remission and alleviating UC symptoms. In the present investigation, we aimed to address the question of whether KJL decoction alleviates the UC symptoms by manipulating the gut microbial structure and function. © FEMS 2020.