The systemic effect of chronic periodontitis (CP) has been suggested by several studies as an etiologic factor and modulator of diseases based on the changes in the inflammatory marker levels. This study aimed to investigate the relationship between the changes in clinical periodontal outcomes and serum biomarkers (CRP, Il-6, albumin and percentage of leukocytes) after non-surgical periodontal therapy in systemically healthy adults. An interventional study was conducted with a sample of 29 individuals without CP (control group) and 33 with CP (CP group). Periodontal clinical variables were recorded, and the serum levels of inflammatory markers were measured. Statistical analysis included the chi-square and Student's t-tests and Pearson's correlation analysis. After 90 days of non-surgical periodontal treatment, a reduction of periodontal parameters and Il-6 in both groups could be observed (P < 0.001). the correlation analysis revealed a directly proportional correlation between changes in the probing depth (r = 0.349, P = 0.049) and clinical attachment level (r = 0.374, P = 0.034) with CRP in the CP group. The findings suggest a reduction of Il-6 serum concentration and periodontal clinical measures 90 days after periodontal therapy in both groups.