Objective  To study the effect of high salt diet (HSD) on oral flora in mice. Methods  Eight C57BL/6J mice were randomly divided into normal salt diet (NSD) group and HSD group. The NSD or HSD model of mice was established with NSD containing 0.4% NaCl or HSD containing 8.0% NaCl. Two weeks after NSD or HSD, the oral ligature wire samples were taken and used for 16S ribosomal RNA gene sequencing. Results  Compared with NSD group, the oral microbiota of HSD group mice had significant changes in species richness and diversity. Compared with NSD group, the results of 16S ribosomal RNA gene sequencing showed that the relative abundance of Lactobacillus and Streptococcus in the oral ligature wire of mice of HSD group was significantly lower, and the relative abundance of Delftia in mice of HSD group was critically higher. Conclusion  HSD can affect the oral microbiota of mice, especially resulting in the reduction of the abundance of Lactobacillus and Streptococcus, and increase of the relative abundance of Delftia.