Efficacy of Ozonated Gels and Oils As Adjunctive or Monotherapy in Periodontitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: This study aimed to evaluate the available clinical evidence on the use of ozonated gels and oils in the management of periodontitis. MATERIAL AND METHODS: Embase, SCOPUS, Web of Science, PubMed, and Google Scholar were searched up to May 13, 2025. Original peer-reviewed randomized controlled trials (RCTs) in English that investigated patients with periodontitis were included. Study characteristics, methods of ozone application, conclusions, and reported complications were extracted. Pooled mean differences of clinical indices were compared between the ozone therapy groups (adjunctive or monotherapy) and control groups (placebo or CHX). Primary outcomes included clinical indices such as probing pocket depth (PPD), plaque index (PI), and gingival index (GI), whereas secondary outcomes comprised clinical attachment level (CAL), clinical attachment loss (CAtL), bleeding on probing (BoP), and sulcus bleeding index (SBI). RESULTS: Of the 962 records, 19 clinical studies were included in the qualitative synthesis and 18 RCTs in the quantitative synthesis. For periodontitis, ozonated compounds significantly reduced PPD when used as an adjunct to subgingival instrumentation (MD = -0.780; p < 0.0001) and reduced clinical attachment loss (CAL) (MD = -0.457; p = 0.001) compared with subgingival instrumentation alone. No statistically significant differences were observed in PI or GI outcomes with ozonated compounds as an adjunct to subgingival instrumentation compared with subgingival instrumentation alone, although sensitivity analyses indicated some instability in the results. Follow-up periods ranged from 4 to 12 weeks across outcomes (8-12 weeks for GI), with most studies reporting 12-week follow-up. No consistent differences were found between ozone and CHX in terms of PPD, CAL, PI or BoP. No adverse effects were reported in the studies. CONCLUSIONS: Ozonated gels and oils were associated with favorable periodontal outcomes, particularly when used as adjuncts to subgingival instrumentation, and no major adverse effects were reported. However, the evidence is limited by short-term follow-up and methodological heterogeneity.