Background: Antibiotic-associated diarrhea (AAD) is of great concern in children due to the wide range of antibiotic administration among this population. Studies considering the use of synbiotics for prevention or treatment of AAD are limited. In the current study, the effectiveness of synbiotics in preventing AAD was investigated. Methods: This randomized, double-blinded clinical trial was conducted on 100 patients undergoing antibiotic therapy for over five days. The patients were randomly divided into a case group receiving synbiotic therapy (Protexin; The United Kingdom) and a control group undergoing placebo therapy (consisting of starch sachets). Both groups began their medication within 24 hours after antibiotic initiation and continued it for further seven days after antibiotic therapy cessation. The two groups were compared regarding the incidence of diarrhea, stool consistency based on the Bristol Stool Scale (BSS), and the duration of diarrhea. Results: The members of case and control groups were not statistically different regarding age, gender distribution, length of hospitalization, the frequency of defecation, and stool consistency based on BSS before antibiotic therapy, primary and final diagnosis, the type of antibiotics prescribed, and duration of antibiotic therapy (P > 0.05). The incidence of AAD was significantly less in the case group compared with the control group (P = 0.016), while those with AAD did not show significant difference regarding the duration of diarrhea, stool consistency based on BSS, and the frequency of defecation a day (P = 0.51, 0.26, and 0.18, respectively). Conclusions: The findings of this study showed that early initiation of synbiotics and its long-term administration following antibiotic therapy cessation could considerably prevent AAD; however, in case of AAD occurrence synbiotic therapy cannot positively affect duration, stool consistency, and the frequency of defecation.