Recent investigations have demonstrated the positive therapeutic effects of omega-3 polyunsaturated fatty acids (PUFAs) on several chronic inflammatory diseases such as rheumatoid arthritis, chronic inflammatory bowel diseases and periodontitis. The objective of the present study was to evaluate the impact of omega-3 PUFAs in conjunction with initial periodontal therapy (IPT) on periodontal clinical parameters and salivary markers in patients with chronic periodontitis. Thirty four systemically healthy individuals with advanced chronic periodontitis were enrolled and randomly assigned into two groups. The control group (IPT, n=17) was treated with IPT alone whereas the test group (IPT+omega-3, n=17) was treated with IPT and daily dietary supplementation of omega-3 PUFAs (in the form of 2 grams of fish oil capsules per day) for three months. Clinical parameters were recorded at baseline and 3 months following therapy for both groups. Saliva samples were collected at the same time points and analyzed for visfatin and tumor necrosis factor-α (TNF-α). After 3 months, clinical periodontal parameters of advanced chronic periodontitis were significantly improved in both groups. The omega-3 group showed significant greater pocket depth (PD) reduction and clinical attachment (CAL) gain compared to the control group after therapy. Salivary TNF-α levels showed a statistically significant decrease in the omega-3 group at 3 months compared to the control group. Salivary visfatin levels were reduced significantly at 3 months in both groups without any significant variation. It was concluded that dietary supplementation with omega-3 PUFAs could be a potential viable adjunct to IPT that significantly improves all periodontal parameters and reduces salivary visfatin and TNF-α levels in advanced chronic periodontitis. Interestingly, salivary visfatin could be a useful periodontal biomarker to monitor responses to periodontal therapy.