BACKGROUND AND OBJECTIVE: Oxidative stress can be described as a state brought on by an unfavorable rise in the generation of reactive oxygen species (ROS), a growth in ROS production, or a decline in antioxidant defense. The study aimed to investigate the impact of non-surgical periodontal treatment on clinical periodontal parameters and serum malondialdehyde MDA, total antioxidant capacity TAOC, and total oxidant status TOS in smokers and non-smokers periodontitis patients. METHODS: A clinical comparative research was carried out on 60 systemically healthy subjects with an average age of 30-50 years; 30 with chronic periodontitis (15 non-smoker periodontitis NSP and 15 smoker periodontitis SP) and 30 with healthy periodontium (15 nonsmoker healthy NSH and 15 smoker healthy SH). Blood samples and clinical periodontal parameters were collected at baseline before scaling & root planing SRP and after six weeks of treatment to estimate MDA, TOS, and TAOC. RESULTS: Clinical periodontal parameters (PI,GI,BOP,PPD&CAL) and oxidative stress markers (MDA and TOS) were significantly reduced after SRP for periodontitis patients groups(smoker periodontitis SP and non-smoker periodontitis NSP) with exception for the nonsignificant reduction of gingival recession GR and non-significant elevation of TAOC (P>0.05 ). However, no correlation was found between biochemical and clinical parameters at baseline and after therapy, except for the significant negative correlation between BOP and TAOC in SP and between TAOC & PPD in NSP before therapy. CONCLUSION: Non-surgical periodontal therapy could significantly improve clinical periodontal parameters, reduce oxidative stress and improve the antioxidant defense system of the body.