Periodontitis is a common multifactorial inflammatory disease with gradual loss of supportive tissues around the teeth which eventually leads to decrease in the quality of life. Blocking Interleukin-6 (IL-6), a multifunctional cytokine with pro-inflammatory properties has demonstrated therapeutic efficacy in inflammatory diseases like Rheumatoid arthritis, SLE and multiple sclerosis. Host immune response, the underlying cause for this progressive disease is targeted by Host modulatory therapy (HMT), an emerging treatment modality. Omega-3 polyunsaturated fatty acids (ώ 3 PUFAs), one of the relatively safe HMTs, reduces tissue destruction, stabilizes or even regenerates the periodontium through its anti-inflammatory & immunoregulatory properties. ώ 3 PUFAs are essential for the synthesis of eicosanoids which are involved in anti-inflammatory, antiplatelet aggregatory, vasodilation, vasoconstriction, immune response, cell growth and proliferation. The key factor examined and extrapolated in this study is the anti-inflammatory property of ώ 3 PUFA. The aim of the study was to evaluate the immunological and clinical response to ώ 3 PUFA supplementation therapy in chronic periodontitis by measuring the inflammatory cytokine, IL-6 levels in serum. In this open label exploratory study, 40 patients with a Female: Male ratio of 4:1were enrolled and assessed clinically by measuring Oral Hygiene Index-Simplified (OHI-S), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL) and their serum for IL-6 levels. Subsequently 300 mg (concentration of EPA 180/DHA120) of ώ 3 PUFA was prescribed twice daily for 3 months and periodically reviewed to assess their IL-6 levels and periodontal status. IL-6 levels which were at a maximum mean of 10.2 pg/ml prior to treatment, showed a gradual and notable reduction to 2.3 pg/ml at the end of the study following ώ 3 PUFA supplementation therapy. The coefficient of variation R2 and ANOVA showed statistically significant periodic variation in biomarker IL-6 and in all clinical measurements at all time intervals. ώ 3 PUFA adjunctive therapy significantly reduces the inflammatory cytokine (IL-6) levels and causes noteworthy improvement of the most relevant clinical parameters (OHI-S, PPD, CAL). Hence ώ 3 PUFA can be recommended as a dietary supplementation and a safe host modulatory treatment in chronic periodontitis.