The present study aimed to estimate the serum levels of vascular cell adhesion molecule-1(VCAM-1), interleukin-6 (IL-6), and lipid profile [including total cholesterol, triglycerides (TGs), high –density lipoprotein cholesterol (HDL) and low –density lipoprotein cholesterol (LDL)] in chronic periodontitis patients and to detect the association between the aforementioned cardiovascular disease risk markers and the periodontal disease severity and extent. In addition, the study also aimed to detect whether the non-surgical periodontal treatment (NSPT) may affect the levels of these biochemical parameters. Fifty eight subjects completed the study and were subdivided into: group I (31 chronic periodontitis patients), and group II (27 adults with clinically healthy gingivae). Group I received standard NSPT. Periodontal parameters and serum levels of VCAM-1, IL-6, and lipid profile were estimated at baseline and at 6 weeks after NSPT. There were significant differences between study groups regarding serum VCAM-1, IL-6, total cholesterol, LDL (p<0.001), and HDL (P<0.05). In group I, the pre-treatment values of all periodontal parameters and biochemical analytes were significantly higher than post-treatment values. At 6 weeks after therapy, both bleeding index and periodontal diseases extension were positively correlated with serum cholesterol, TGs, and LDL. BI was negatively correlated with HDL. It was concluded from the previous findings that chronic periodontitis has the potential to increase systemic inflammation, vascular endothelial biomarkers, and serum lipid profile of affected individuals. Hence, NSPT may reduce the risk of CVS diseases by reducing the systemic inflammation.