The aim of this study was to investigate the effects of an extract of Qiweibaizhu powder combined with Debaryomyces hansenii on the gut microbiota of antibiotic-treated mice with diarrhea. Mice were gavaged with a mixture of gentamycin sulfate and cefradine to induce diarrhea. After diarrhea was observed, 25% dose of ultra-micro Qiweibaizhu powder extract combined with 25% dose of Debaryomyces hansenii (QCD) was gavaged to mice with diarrhea. DNA of intestinal contents in mice was extracted for 16S rRNA gene sequence analysis by high-throughput sequencing following treatment finished. The results showed that the QCD increased the species richness and diversity, but did not recover the diversity to the original level. Antibiotics and QCD significantly altered the composition of gut microbiota at different taxonomic levels. At the genus level, the relative abundance of Bacteroidales S24-7 group_unidentified and Bacteroides returned to baseline after QCD treatment. Additionally, QCD suppressed the growth of Oscillospira and Ruminococcus, and promoted the proliferation of Erysipelotrichaceae_norank and Blautia compared with the healthy and diarrheal mice. Our results indicated that QCD modulated the diversity and composition of the gut microbiota in antibiotic-treated mice with diarrhea. The synergistic effect between Qiweibaizhu powder extract and Debaryomyces hansenii may be related to Bifidobacterium and Bacteroidales S24-7 group_unidentified.