This study aimed to identify the oral microbial signature of Kazakh female rheumatoid arthritis (RA) patients. A total of 75 female patients who met the American College of Rheumatology 2010 classification criteria for RA and 114 healthy volunteers were included in the study. Amplicons of the 16S rRNA gene were sequenced to analyze the microbial composition. We identified significant differences in bacterial diversity and abundance between the RA and control groups, as measured by Shannon (pvalue = 0.0205) and Simpson (pvalue = 0.00152) indices. The oral samples from RA patients had higher bacterial diversity than those from non-RA volunteers. The RA samples had a higher relative abundance ofPrevotellaceaeandLeptotrichiaceae, but a lower content of butyrate and propionate-producing bacteria compared to the control group. The samples from patients in remission had a higher abundance of Treponema sp. andAbsconditabacteriales(SR1), whereas those with low disease activity had higher levels ofPorphyromonasand those with high RA activity had higher levels of Staphylococcus. A positive correlation was found between the taxa Prevotella_9 and serum levels of antibodies to cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF). The predicted functional pattern of the ACPA+/RF− and ACPA+/RF+ seropositive groups was characterized by increased ascorbate metabolism, degradation of glycosaminoglycans, and reduced biodegradation of xenobiotics. These findings suggest that the functional pattern of the microflora should be considered when selecting a therapeutic strategy for RA in order to provide a personalized approach.