Low-density lipoprotein (LDL) is formed during the oxidation process, and the damages resulting from these oxidative reactions lead to the development of cardiovascular diseases. Paraoxonase 1, a calcium-dependent enzyme bound to high-density lipoprotein (HDL). The aim of this study was to isolate LDL and investigate the fractions obtained from the alcoholic extract of Aqaqia root to assess their impact on oxidation LDL and paraoxonase 1 activity under in vitro conditions. Blood samples were obtained from healthy individuals after an overnight fast and their serum was separated using ultracentrifugation with a medium gradient. LDL samples were subjected to copper sulfate oxidation, and the kinetics related to LDL oxidation, inhibition of conjugated DNA formation, as well as paraoxonase enzyme activity in the presence of polyphenolic components from gel filtration chromatography of Aqaqia root extract, were examined. The oxidation of LDL under the influence of polyphenolic components derived from gel filtration chromatography of Aqaqia root extract resulted in a significant reduction and also lead to the inhibition of conjugated DNA formation, a secondary product of lipid peroxidation. However, it did not show a significant increase in paraoxonase enzyme activity. Findings indicated that phenolic compounds obtained from gel filtration chromatography of Aqaqia root extract were effective in reducing the LDL oxidation process and diminishing the production of conjugated DNA compared to the control sample. These compounds have the potential to be effective in preventing oxidative-related diseases including atherosclerosis.