Non-surgical periodontal therapy (NSPT) has been shown to have systemic effects. It has been suggested that, similar to rheumatoid arthritis (RA), periodontitis (PD) has an impact on general health, in terms of psychological, physical, and social aspects. This study determines the effect of periodontal treatment in RA activity, health-related quality of life, and oral health self-perception before and after periodontal treatment in RA patients. A quasi-experimental, prospective, non-randomized study was conducted, and 52 patients were included in the study. Periodontal parameters and the instruments disease activity score-28 (DAS-28), SF-36, and OHIP-14 were measured at baseline and at 3 months after NSPT. All differences were statistically assessed. The study protocol was registered in Clinical Trials (NCT04658615). No statistically significant differences were found in the scores of DAS-28 before and after the intervention in the group with PD and reduced periodontium. When the effect of periodontal treatment was analyzed in the group of 29 patients who were followed up, it was found that there were statistically significant differences before and after in variables such as psychological distress, emotional role, and mental health, which indicates an improvement in the scores of these variables. NSPT influenced the health-related quality of life measured with SF-36 and OHIP-14 in patients with RA. In conclusion, NSPT has an effect on self-reported quality of life and health indicators more than the RA activity as measured with DAS-28. However, the clinical effect of periodontal treatment in RA patients provides important data to support periodontal care in patients.