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Simple Summary: Gut microbiota homeostasis is significant to host health and well-being. Treatment of red-crowned cranes with avian influenza vaccines and anthelmintics has played pivotal roles in therapeutic management in zoos. This study provides evidence concerning if and how the avian influenza vaccine and anthelmintic treatment impact the gut microbiota of red-crowned cranes. For the first time, we revealed that the gut microbiota of red-crowned cranes is resilient to the avian influenza vaccine and anthelmintic, which may be affected to disorder in the short term but can recover to homeostasis over time. In addition, it is proposed that more controlled experiments should be performed properly to contribute to animal disease control and optimal management in the zoo. Gut microbiota homeostasis is important for host health and well-being; however, drugs may affect the composition and function of the gut microbiota. Red-crowned cranes are a vulnerable species. Treatment of red-crowned cranes with avian influenza vaccines and anthelmintics has played pivotal roles in therapeutic management in zoos. To investigate the changes in the diversity and composition of gut microbiota after the avian influenza vaccine and anthelmintic treatment, we used 16S rRNA sequencing to obtain and compare the bacterial community composition before and after the treatment. The alpha diversity of the gut microbiota of red-crowned cranes decreased on the day of the treatment and then fluctuated over time. The composition of gut microbiota tended to be similar in the short term after the treatment, as supported by the beta diversity hierarchical cluster analysis. Only 3, 8, and 72 operational taxonomic units (OTUs) of the three individuals were shared among the five groups before and after treatment. The relative abundance of Firmicutes significantly increased to 99.04% ± 0.28% on the day of the treatment, in which the relative abundance of Lactobacillus was 93.33% ± 5.85%. KEGG pathways analysis indicated that the main function of the gut microbiota is involved in metabolism, and the present study indicates that the gut microbiota of red-crowned cranes is resilient to the avian influenza vaccine and anthelmintic, even disordered in the short term, and could recover over time. More individual experimentation and functional potential in metabolism are needed in the future to support animal disease control and optimal management in the zoo. [ABSTRACT FROM AUTHOR]