Although the use of ozone therapy in dentistry has become widespread, the number of controlled clinical trials evaluating its effectiveness in periodontal therapy is limited. The aim of this study was to evaluate the efficacy of ozone treatment, that is used in concert with scaling and root planning (SRP), on clinical periodontal parameters and to analyze its effect on cytokine levels of GCF in aggressive periodontitis patients. Totally, 27 patients with aggressive periodontitis were randomly selected into groups of treatment with either subgingival SRP followed by application of ozone with a periodontal probe (SRP+ozone) or subgingival SRP followed by irrigation with serum irrigation (SRP-control). The following parameters were evaluated at baseline (T0), and 6 weeks (T1): plaque index (PI); gingival index (GI); probing pocket depth (PPD), clinical attachment loss (CAL), GCF volume, GCF Interleukin-1 beta (IL-1 beta), and GCF Interleukin-10 (IL-10) cytokine levels. There was a significant difference in terms of clinical periodontal parameters before and after treatment in both groups. When comparing between groups, there was no significant difference between the treatment methods after 6 weeks with respect to the PI, PPD, CAL, and GCF IL-10 levels. In contrast, GI, GCF volume, and GCF IL-1 beta levels were statistically significantly different between the two groups at the 6th week after treatment. Application of ozone as an adjunctive therapy to SRP was shown to provide a statistically significant improvement in treatment results compared to SRP plus serum irrigation.