Abstract: Background　The gut microbiota may mediate cognitive impairment associated with periodontitis, but there is no direct evidence indicating whether modulating the gut microbiota can ameliorate such impairment.Objective　This study aimed to investigate the effects of fecal microbiota transplantation (FMT) on cognitive function and gut microbiota in experimental periodontitis mice and to elucidate the mechanisms by which gut microbiota influences periodontitis-related cognitive decline. Methods　C57BL/6 mice were randomly divided into four groups (n=12 per group): control group (C), periodontitis group (P), periodontitis + control FMT group (C-P), and control + periodontitis FMT group (P-C). Experimental periodontitis was induced by silk ligation. After 8 weeks, fecal microbiota suspensions were administered via gavage every other day for 2 weeks. Anxiety-like behavior and cognitive function were assessed using open field test, novel object recognition test, and Y-maze test. Fecal samples were collected for 16S rRNA gene sequencing to analyze changes in gut microbiota. Serum and brain levels of tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA. The expression of blood-brain barrier tight junction proteins ZO-1 and Occludin was detected by Western blot.Results　Periodontitis induction led to alveolar bone resorption in mice (P＜0.001) and impaired spatial working memory and object recognition (P＜0.05). Meanwhile, serum and brain levels of TNF-α and IL-1β were increased in the periodontitis group (P＜0.05), while the expression of blood-brain barrier tight junction proteins ZO-1 and Occludin was decreased (P＜0.05). 16S rRNA sequencing revealed an increased abundance of Muribaculum and Colidextribacter genera in the gut microbiota of periodontitis mice (P＜0.05). FMT treatment improved alveolar bone resorption (P＜0.001) and cognitive function (P＜0.05) in periodontitis mice, reduced inflammatory cytokine levels (P＜0.01), and restored blood-brain barrier integrity (P＜0.05). Conclusion　FMT may ameliorate periodontitis-related cognitive decline by modulating gut microbiota balance, reducing systemic and brain inflammation, and repairing blood-brain barrier damage.