This study is aimed at investigating the impact of mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules on intestinal mucosa barrier function and intestinal microbiota in mildly active Crohn's disease patients. Ninety-six Crohn's disease patients in mild activity period were randomized into the control group (treated with mesalamine) and the observation group (treated with mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules) ( = 48). After 4 wk of treatment, the patients were evaluated for their clinical efficacy. Intestinal microbiota counts, serum inflammatory factors, T lymphocyte subsets, and mucosal barrier function indicators in both groups were assessed. After 4 wk of treatment, the total clinical effective rate of the observation group was higher than that of the control group. The number of () and () in the intestinal tract, serum IL-10 levels, and peripheral blood CD4+ and CD4+/CD8+ levels were higher, and the number of (), the levels of TNF-α, IL-6, CRP, CD8+, ET, D-lactate, DAO, and urine L/M ratio were lower in the observation group in comparison to those in the control group (all  < 0.05). Mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules are more effective in treating mildly active Crohn's disease.