Objective To analyze the efficacy and related mechanism of Clostridium Butyricum Powder combined with domperidone in the treatment of children with functional dyspepsia (FD).Methods A total of 144 children with FD who were treated in Hefei First People's Hospital from March 2019 to July 2020 were divided into two groups according to the random number table. The two groups of children were both given routine supportive treatments such as adjusting diets, establishing good bowel habits, preventing and correcting water-electrolyte and acid-base imbalance. Besides, the control group received domperidone treatment, and the combination group took Clostridium Butyricum Powder plus domperidone. All treatments lasted for 1 week. The efficacy and safety of medication in the two groups were evaluated, and the changes in gastric kinetics, brain-gut axis related factors [5-hydroxytryptamine (5-HT), neuropeptide S receptor 1 (NPSR1), substance P (SP)], and gastrointestinal hormones [somatostatin (SST), motilin (MTL), gastrin (GAS), leptin] after the treatments were observed.Results The overall effective rate of the treatment in the combination group (91.67%) was higher than that of the control group (79.17%) (P < 0.05). The differences in contraction amplitude, contraction frequency and motility index of gastric antrum before and after the treatments were higher in the control group than those of the combination group (P < 0.05). The changes of 5-HT and SP levels in the control group were lower than those in the combination group after treatment, while the difference in NPSR1 level before and after the treatments was higher in the control group compared with the combination group (P < 0.05). Besides, in comparison with the control group, the differences in levels of MTL and GAS were lower but those in levels of SST and leptin were higher in the combination group (P < 0.05). The incidence of adverse reactions in the combined group (9.72%) was comparable to that in the control group (4.17%) (P >0.05).Conclusions Clostridium Butyricum Powder combined with domperidone has a definite effect in the treatment of children with FD, and does not significantly increase the adverse reactions. Its mechanism of action may be related to the improvement of gastric kinetics, and the regulation of brain-gut axis associated factors and gastrointestinal hormone levels.