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INTRODUCTION Diabetes mellitus is the most common metabolic disorder in humans, and its incidence is increasing rapidly worldwide. Although polyunsaturated fatty acids have beneficial effects on diabetes mellitus, previous data regarding the possible positive effects of n-3 fatty acids on glycaemic indices were inconclusive. We conducted a double-blind randomised clinical trial to determine the effects of eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, on overweight patients with type 2 diabetes mellitus (T2DM). MeThODs This double-blind, placebo-controlled randomised clinical trial was conducted on a total of 67 overweight patients with T2DM for a duration of three months. Of these 67 patients, 32 received 2 g purified EPA daily, while 35 received a placebo of 2 g corn oil daily. The patients’ fasting plasma glucose (FPG), serum insulin, glycated haemoglobin (HbA1c) and insulin sensitivity indices were assessed. ResUlTs After three months of EPA supplementation, the group that received EPA showed significant decreases in FPG (p< 0.001), HbA1c (p= 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR)(p= 0.032), when compared to the placebo group. EPA supplementation resulted in decreased serum insulin levels, with the levels between the EPA and placebo groups showing a significant difference (p= 0.004). CONClUsION The results of our study indicate that EPA supplementation could improve insulin sensitivity. It was able to decrease serum insulin, FPG, HbA1c and HOMA-IR. EPA could have beneficial effects on glycaemic indices in patients with T2DM.