We assessed the effect of a 2-year supplementation with a highly concentrated docosahexaenoic acid (DHA) product with antioxidant activity on non-proliferative diabetic retinopathy (NPDR) in a randomized double-blind placebo-controlled study. A total of 170 patients with diabetes were randomly assigned to the DHA group (n = 83) or the placebo group (n = 87). NPDR was diagnosed using non-contact slit lamp biomicroscopy examination, and classified into mild, moderate, and severe stages. Patients in the DHA group received a high rich DHA triglyceride (1050 mg/day) nutritional supplement, and those in the placebo group received olive oil capsules. The percentages of mild NPDR increased from 61.7% at baseline to 75.7% at the end of the study in the DHA group, and from 61.9% to 73.1% in the placebo group. Moderate NPDR stages decreased from 35.1% at baseline to 18.7% at the end of the study in the DHA group, and from 36.8% to 26.0% in the placebo group. In the DHA group, there were five eyes with severe NPDR at baseline, which increased to one more at the end of the study. In the placebo group, of two eyes with severe NPDR at baseline, one eye remained at the end of the study. Changes in visual acuity were not found. There were improvements in the serum levels of HbA1c in both groups, but significant differences between the DHA and the placebo groups were not found. In this study, the use of a DHA triglyceride nutraceutical supplement for 2 years did not appear to influence the slowing of the progression of NPDR.