We determined the polyphenol content in a defined volume of chemically characterized and standardized propolis sample to evaluate its effectiveness in patients with chronic periodontitis. 150 patients were enrolled, randomly divided into three groups and subjected to three different treatments, Scaling and Root planing (SRP) associated with propolis, SRP with 1% chlorhexidine gel and SRP only. Before the treatments, Full Mouth Plaque Score (FMPS), Pocket Depth at Probing (PPD), Full Mouth Bleeding Score (FMBS), Impaired furcations according to the Hamp Classification, Mobility, Gingival recession and Clinical Attack Level (CAL) were evaluated. A significant reduction of all the studied variables was observed in the three examined groups even if in the group treated with propolis, after 6 weeks, the reduction, and therefore the improvement, was higher than SRP treatment alone and in the presence of 1% chlorhexidine gel. Finally, there were no significant differences in the reduction of PPD and CAL between the groups treated with chlorhexidine and the group treated with SRP alone. Compared to the other two groups, Subjects treated with 10.4 mg propolis showed a significant improvement in all four variables. This study shows that propolis could be used as a natural adjuvant in the treatment of periodontal disease.