Dietary garlic has been shown to alleviate hypercholesterolemia, a condition associated with the development of cardiovascular disease. Reactive oxygen species take part in the disease progression, but it is unknown if antioxidant rich garlic arrests lipid and cholesterol oxidation in hypercholesterolemia. This study provides fermented garlic or non‐fermented garlic to mild hypercholesterolemia (total cholesterol: 5.2–6.2 mmol L−1) and determines its ability to relieve in vivo oxidative stress by measuring multiple oxidized lipid products of polyunsaturated fatty acid (PUFA) and cholesterol oxidation products (COPs) in plasma. Plasma fatty acids levels are also analyzed. After 13 weeks supplementation, both groups show a significant increase in α‐linolenic acid level (p < 0.05). Levels of arachidic acid increase and palmitoleic acid decreases in the group supplemented with non‐fermented garlic. Of the oxidized PUFA products, notably those derived from enzymatic oxidation of arachidonic acid, namely hydroxyeicosatetraenoic acid (HETE), show a significant difference. Levels of lipoxygenase mediate 5‐HETE and 12‐HETE, and CYP‐P450 mediates 9‐HETE and 11‐HETE decreases after non‐fermented garlic supplementation only (p < 0.05). Non‐enzymatic PUFA oxidation and COPs are not altered by garlic supplementation. Overall, only non‐fermented garlic intake shows selective antioxidant properties in mild hypercholesterolemia where limited effect is found in reducing lipid oxidation.Practical Applications: Current research provides a new insight for the use of garlic extract as a nutraceutical to reduce in vivo oxidative stress. The modified enzymatic oxidation of arachidonic acid in mild hypercholesterolemia after non‐fermented garlic extract intake potentially preventes the progression of chronic inflammation that can lead to complicated pathologies such as arthritis, cardiovascular diseases, and non‐alcoholic fatty liver disease.Garlic is a claimed functional food. The fermented form is proposed to have stronger antioxidant properties. Analysis of mild hypercholesterolemia plasma before and after fermented or non‐fermented garlic extract intake for 13 weeks revealed augmented α‐linolenic acid. Garlic appeared to be selective in the antioxidant property. Pro‐inflammatory lipid mediators (5‐, 9‐, 11‐, and 12‐HETE) released via enzymatic polyunsaturated fatty acid (PUFA) oxidation reduced after non‐fermented garlic extract intake only. However, intake of both garlic types did not reduce non‐enzymatic PUFA oxidation status.