High calorie and fat consumption and the production of free radicals are two major mechanistic pathways between diet and disease. In this study we evaluated the effect of a plant-based diet poor in animal fat and rich in (n-3) fatty acids on fatty acids of serum phospholipids and on the production of reactive oxygen metabolites (ROMs). One hundred and four healthy female postmenopausal volunteers were recruited and randomized to a dietary intervention or a control group. Dietary intervention included a program of food education and biweekly common meals for 18 weeks. When the intervention and control groups were compared, it was seen that dietary intervention resulted in a significant reduction of saturated fatty acids (-1.5%) and a significant increase in (n-3) fatty acids (+20.6%), in particular docosahexaenoic acid (+24.8%). We observed that arachidonic acid decreased (–7.7%), while (n-6) fatty acids did not, and the (n-3)/(n-6) polyunsaturated ratio increased significantly (+24.1%). As expected, ROMs decreased significantly in the intervention group (-6%). The results indicated that a plant-based diet can improve the serum fatty acid profile and decrease ROMs production. These results suggest that a plant-based diet may reduce the body's exposure to oxidative stress.