Context: Periodontitis and diabetes are universally prevalent diseases which are interlinked with each other. Inflammatory products released both by the microorganisms, and the host plays a pivotal role in causing both the diseases. Pentraxins are acute-phase proteins which are often found to be elevated in inflammatory states. Anti-inflammatory agents have a very important role to play in curbing infection of which, aspirin and omega-3 fatty acids (O3FAs) are being administered often nowadays. Nonsurgical periodontal therapy (NSPT) remains the gold standard of treatment, and other agents have been used as adjuvants only, to increase the efficacy of treatment. Aims: This study compares the effects of low-dose aspirin versus O3FAs when used as adjuvants to NSPT in patients with diabetes and chronic periodontitis. Settings and Design: A total of 42 patients (mean age of 30–65 years) from a diabetic center who were diagnosed with Type II diabetes and chronic periodontitis were included in the study. Materials and Methods: This study was done in the department of periodontics of a tertiary referral care hospital in Hyderabad, in collaboration with a reputed diabetic center. Statistical Analysis Used: Intragroup comparison was done using the paired t -test for continuous data and Wilcoxon signed-rank test for score data. Intergroup comparison was compiled using independent t -test. All P < 0.05 were considered statistically significant. Results: Intragroup comparison at baseline and 3 months after NSPT showed statistically significant results ( P < 0.001) in all the three groups pertaining to the clinical (gingival index, probing pocket depth, and clinical attachment level) and biochemical (glycosylated hemoglobin and pentraxin) parameters. However, the intergroup comparison showed a significant improvement in Group II related to pentraxin levels only ( P < 0.001). Conclusions: O3FAs proved to be better than low-dose aspirin and placebo after NSPT.