| Summary: | (1) Background: The aim of this split-mouth design study was to analyze the clinical periodontal indexes and oxidative stress markers in gingival crevicular fluid modifications after three periodontal disease treatment possibilities (scaling and root planning—SRP; SRP and diode laser—L; SRP and photodynamic therapy—PDT). (2) Methods: The study was conducted on 52 patients: systemically healthy subjects with periodontal disease—non-RA (<i>n</i> = 26); and test group (<i>n</i> = 26) subjects with rheumatoid arthritis and periodontal disease—RA. Clinical periodontal measurements (probing depth—PD; Löe and Silness gingival index—GI; papillary bleeding index—PBI; and periodontal community index of treatment needs—CPITN) and oxidative stress markers (8-hydroxy-2’-deoxyguanosine (8-OHdG) and 4 hydroxynonenal (4-HNE)) were analyzed at baseline (T0), after three sessions of periodontal treatment (T1), and 6 months after treatment (T2). (3) Results: Periodontal therapy improved clinical periodontal measurements and oxidative stress markers in both analyzed groups, with supplementary benefits for laser- and PDT-treated periodontal pockets. (4) Conclusions: The analyzed oxidative stress markers decreased significantly following non-surgical periodontal therapy in both rheumatoid arthritis and systemically healthy patients. All the periodontal disease treatment possibilities analyzed in this study offered clinical and paraclinical improvements; however, the association of laser with SRP and photodisinfection with SRP yielded the best clinical and paraclinical outcomes when compared to SRP alone.
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