Objective To investigate the synergistic preventive effect of Saccharomyces boulardii combined with Bifidobacterium quadruple viable preparation (BQP) on antibiotic-associated diarrhea (AAD) in infants and young children, aiming to provide evidence for optimizing probiotic intervention strategies in clinical practice. Methods A prospective, randomized, parallel controlled trial enrolled hospitalized children aged 1-36 months requiring antibiotic treatment from October 2023 to June 2025. Participants were randomly assigned to four groups: control (no probiotic; n=59), Saccharomyces boulardii (Saccharomyces boulardii powder; n=59), BQP (BQP tablets; n=58), and combined group (Saccharomyces boulardii powder plus BQP tablets; n=60). Probiotic interventions were administered from antibiotic initiation until 7 days after discontinuation. The primary outcome was the incidence of AAD during treatment. Secondary outcomes included diarrhea duration, fecal microbiota composition (16S rRNA sequencing), inflammatory markers (fecal calprotectin, serum interleukin-6), and safety. Follow-up continued until 30 days after probiotic cessation. Results The combined group showed a significantly lower AAD incidence (7%) compared to the Saccharomyces boulardii group (15%), BQP group (17%), and control group (31%) (P<0.0083). On the 30th day after probiotic cessation, the combined group demonstrated a significantly higher Shannon diversity index than the other three groups (P<0.05); relative abundances of Bifidobacterium and Lactobacillus in feces were significantly higher in the combined group than the other three groups (P<0.05), while the relative abundances of Enterococcus weresignificantly lower than in the other three groups (P<0.05). On the 7th day after antibiotic cessation, the combined group showed significantly lower levels of inflammatory markers compared to the other three groups (P<0.05). Adverse event rates did not differ significantly among groups (P>0.05). Conclusions The combination of Saccharomyces boulardii and BQP prevents AAD in infants and young children more effectively than a single probiotic regimen, potentially through synergistic enhancement of beneficial bacterial colonization and accelerated gut microbiota restoration. This combined probiotic regimen warrants clinical promotion.