Abstract Oxidative modification of low‐density lipoproteins (LDL) and high‐density lipoproteins (HDL) are important factors determining cardiovascular risk. This study investigated the antioxidant mechanisms and potential protective effect of a hydroethanolic extract of yerba mate ( Ilex paraguaiensis ; EHEM) on the in vitro oxidation of LDL and HDL. EHEM was found to possess ferric reducing power, DPPH free radical scavenging capacity, metal chelating activity, and NO radical scavenging activity. In addition, EHEM reduced the lipoperoxidation induced by α,α′‐Azodiisobutyramidine dihydrochloride (AAPH) in HDL and LDL at all tested concentrations. In this study, we demonstrate the antioxidant properties of yerba mate and its phytochemical compounds. These properties may effectively prevent the in vitro oxidation of LDL and HDL molecules, a phenomenon linked to the pathogenesis of atherosclerosis.