The present study investigated the effect of non-surgical periodontal therapy on serum level of anti-cardiolipin antibodies (aCLA), which are potentially involved in the pathogenesis of cardiovascular diseases in periodontal patients. Twenty volunteers (11 females and 9 males) with the mean age of 40.55 years participated in this study. Generalized chronic periodontitis was diagnosed through clinical periodontal examination at baseline visit. This examination included measuring the probing pocket depth and clinical attachment loss. Plaque index and gingival index were also recorded. After baseline examination, all the subjects received full-mouth non-surgical periodontal treatment. Subjects returned for a final visit 6 weeks after the last session of scaling for reevaluation of the periodontal parameters. At baseline and final visits 2 ml of venous blood was collected from each patient and an available commercially enzyme-linked immunosorbent assay was used for analyzing aCLA (IgM and IgG). The collected data were analyzed using the paired sample t test. Mean levels of both forms of aCLA, before and after treatment, showed statistically significant difference (P = 0.003 for IgM and P = 0.001 for IgG). In addition, study results showed significant reductions in periodontal parameters after non-surgical periodontal therapy (P < 0.001). The results of this study suggested that successful periodontal therapy can improve the serum level of one of the inflammatory biomarkers involved in the cardiovascular problems.