Genes have been implicated in the levels of oxidative stress, lipids, CVD risk, immune reactivity, and performance. Pequi oil (Caryocar brasiliense) has shown anti-inflammatory and hypotensive effects, besides reducing exercise-induced DNA, tissue damages, and anisocytosis. Given that diet can interact with the human genome to influence health and disease, and because genetic variability can influence response to diet, we aim to investigate the influence of 12 gene polymorphisms on inflammatory markers, postprandial lipids, arterial pressure, and plasma lipid peroxidation of runners (N = 125), before and after 14 days of 400 mg pequi-oil supplementation, after races under closely comparable conditions. Arterial pressure was checked before races; blood samples were taken immediately after racing to perform leukogram and plateletgram, Tbars assay, lipid, and CRP dosages and genotyping. CAT, GST-M1/T1, CRP-G1059C, and MTHFR-C677T polymorphisms influenced post-pequi-oil responses in leukogram; Hp and MTHFR-C677T, in plateletgram; Hp, ACE, GSTT1, and MTHFR-A1298C, in lipid profile; MTHFR-A1298C, in C-reactive protein (CRP) levels; and Hp and MnSOD, in Tbars assay. Differences between ACE genotypes in leukogram and total cholesterol disappeared after pequi, and the same occurred for Hp and MnSOD in Tbars assay and for MTHFR-A1298C with CRP levels. Because genetic inheritance is one of the factors that drive atherosclerosis-related lipid abnormalities, results can contribute to a greater understanding of the influence of genetic polymorphisms in situations that push up free radicals. Knowledge is also expanded on how antioxidant supplementation affects an individual's genes and how athletic genetic makeup can affect the way a person responds to antioxidant supplements.