Abstract: Objective：To investigate the efficacy and safety of oryz-aspergillus enzyme and pancreatin tablet combined with trimebutine maleate tablet on functional diarrhea （FD）. Methods： According to the Rome Ⅲ Diagnostic Criteria for FD, the patients were recruited from Zhongshan Hospital, affiliated to Fudan University, Shanghai, China. These patients were randomly divided into the combination therapy group and the monotherapy group. The patients in the combination group were prescribed with oryz-aspergillus enzyme and pancreatin tablet (2 pellets with a meal, three times a day) and trimebutine maleate tablet (1 pellet post-meal, three times a day) for 4 weeks, and the patients in the monotherapy group were prescribed with trimebutine maleate tablet (1 pellet post-meal, three times a day) for 4 weeks. The efficacy and safety of the drugs were evaluated. Results： After 4 weeks, the overall efficacy rate of the combination therapy on FD was superior to that of the monotherapy (88.9% vs 80.9%，P=0.01). Additionally, the cure rate and the significant efficiency rate of the combination therapy on FD were also both superior to that of the monotherapy (29.6% vs 14.9% and 51.9% vs 31.9%, P<0.01). After withdrew, the recurrence rate of diarrhea was significantly higher in the monotherapy group than in the combination group (4.3% vs 18.4%，P=0.002). None of the patients reported the drug-related adverse effects during the study. Conclusions：The oryz-aspergillus enzyme and pancreatin tablet can improve the effect of trimebutine maleate tablet on FD. FD can be effectively treated by the combination with these two drugs.