The primary and secondary aims of the present study were to prospectively evaluate in a cohort of patients with a diagnosis of periodontitis: (1) the efficacy of non-surgical periodontal therapy assisted by the use of ozonated olive oil-based mouthwash on salivary metalloproteinase (MMP-8) values and (2) the reduction of periodontal indices. This evidence concerns the gene MMP8 and periodontitis.