Abstract: The aim of this study was to investigate the protective effects of camel milk (CM) fermented by Lactiplantibacillus plantarum (L. plantarum) XT016 on DSS-induced colitis, which provided new theoretical basis for the CM application in Xinjiang. The DSS-induced ulcerative colitis mouse model was established. ICR male mice were randomly divided into five groups over a 14-day experimental period: The control group, the model group, the camel milk group, and the fermented camel milk inoculated by L. plantarum XT016 and Lacticaseibacillus casei Shirota (LcS) group. The H&E staining was used to observe the morphology of the mouse colon, and ELISA was used to detect inflammatory factors (IL-6, IL-8, IL-10, TNF-α, TGF-β). 16S rRNA high-throughput sequencing technology was employed to analyze changes in the intestinal microbiota of mice. The results showed that compared with the model group, XT016 fermented camel milk improved the severity of DSS-induced colitis, including reducing body weight, shortening colon length, and lowering DAI scores, effectively reducing pro-inflammatory factors (IL-6, TNF-α) and increasing the levels of anti-inflammatory factors (IL-10, TGF-β). After intervention with XT016 fermented camel milk, the ratio of Firmicutes and Bacteroidetes in the mouse gut microbiota regualted, while the relative abundance of beneficial bacteria such as Lactobacillus and Ruminococcaceae increased, and the relative abundance of Prevotellaceae and Helicobacter decreased. Conclusion: Lactiplantibacillus plantarum XT016 fermented camel milk has a potential role in alleviating ulcerative colitis in mice and can regulate the gut microbiota balance in mice with ulcerative colitis.