Type 2 diabetes mellitus (T2DM) and metabolic syndrome contribute to hypertriglyceridemia, which may increase residual risk of cardiovascular disease in patients with elevated triglyceride (TG) levels despite optimal low-density lipoprotein cholesterol (LDL-C) levels with statin therapy. Prescription products containing the long-chain omega-3 fatty acids (OM3FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are an effective strategy for reducing TG levels. These products are well tolerated and can be used safely with statins. Randomized controlled trials have demonstrated that all prescription OM3FAs produce statistically significant reductions in TG levels compared with placebo; however, differential effects on LDL-C levels have been reported. Products containing DHA may increase LDL-C levels, whereas the EPA-only product did not increase LDL-C levels compared with placebo. Available data on the effects of OM3FAs in patients with diabetes and/or metabolic syndrome support that these products can be used safely in patients with T2DM and have beneficial effects on atherogenic parameters; in particular, the EPA-only prescription product significantly reduced TG, non-high-density lipoprotein cholesterol, Apo B, remnant lipoprotein cholesterol, and high-sensitivity CRP levels without increasing LDL-C levels compared with placebo.