Objective <p>The association between oral microbiome diversity and rheumatoid arthritis (RA) remains unclear. This study aims to investigate&#xa0;the association between oral microbiome diversity and RA.</p> Methods <p>In this nationwide cross-sectional study, 5284 participants from the 2009–2012 National Health and Nutrition Examination Survey (NHANES) cycles were included. To explore the potential association between α-diversity and self-reported RA, weighted logistic regression and weighted restricted cubic spline (RCS) analyses were carried out. Subgroup analysis was performed to examine the robustness of the results. Finally, β-diversity in non-RA and RA groups was examined using principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA).</p> Results <p>Our findings suggested that α-diversity was negatively correlated with RA, and the subsequent RCS analysis supported that the lower the variety of bacteria, the higher the likelihood of having RA. In the subgroup analysis, no apparent interaction effect was detected. PCoA and PERMANOVA demonstrated significant differences in the composition of the oral microbiome between non-RA and RA groups in terms of β-diversity.</p> Conclusion <p>Oral microbiome diversity was significantly associated with RA. This finding may offer new clinical insights into the treatment and prevention of RA, while also enhancing our understanding of its relationship with periodontitis.</p> <p><Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> <p>Key Points</p> <p>• By utilizing NHANES data, this study reveals the association between oral microbiome diversity and RA.</p> <p>• Lower α-diversity was closely related to higher RA prevalence.</p> <p>• PCoA and PERMANOVA showed that β-diversity differed in non-RA and RA groups.</p> </entry> </row> </tbody> </tgroup> </Table></p>