Objectives: Cranberries, high in polyphenols, have been associated with a favorable glycemic response in patients with type 2 diabetes and also are beneficial for oral health. Because type 2 diabetes mellitus and periodontal disease have a physiological relationship, this study aimed to evaluate the hypothesis that cranberry juice enriched with omega-3 will improve glycemic and lipid profiles and periodontal status in patients with diabetes with periodontal disease. Materials and Methods: In this randomized clinical trial, 41 patients with diabetes (age 35-67 years) with periodontal disease were recruited and randomly assigned to 4 groups: control (C; n=12), receiving omega-3 (I1; n=10, 1 g/twice daily), cranberry juice (I2; n=9, 200 ml, twice daily), and cranberry juice enriched with omega-3 (I3; n=10, 200 ml, containing 1 g omega-3) twice daily for 8 weeks. Nonsurgical periodontal therapy was provided for all patients during the study. Fasting blood glucose and glycated hemoglobin, lipid profile, probing depth, anthropometric indices, and 3-day 24-hour dietary recalls were measured pre- and postintervention. Results: Glycated hemoglobin was decreased significantly in I1 and I3 groups. Serum high-density lipoprotein cholesterol (HDL-C) levels increased significantly in the I3 group compared to baseline and compared to I1 and I2 groups. Probing depth was significantly reduced in all groups postintervention. Conclusion: Consumption of cranberry juice enriched with omega-3 can be beneficial as adjuvant therapy with nonsurgical periodontal therapy in decreasing glycated hemoglobin, increasing HDL-C, and improving periodontal status in patients with diabetes with periodontal disease.