Research into the oxidation of lipoprotein has yielded many insights into the underlying process of the development of atherosclerosis. Oxidative modification of low density lipoprotein (LDL) has been suggested as an initial step in the pathogenesis of atherosclerosis. However, up until now, investigations of antioxidants have mostly focused on three main dietary antioxidant vitamins (β-carotene, vitamin C, and vitamin E) and some synthetic compounds. Among those antioxidants, probucol, a synthetic compound, has been shown to be an extremely potent and effective antioxidant in preventing the formation of atherosclerosis in both in vitro and in vivo studies. The present review focuses on commonly used analytical methods for measuring the antioxidant potency and outlines the critical steps on how to evaluate and design a potent antioxidant agent that can be used for the intervention of atherosclerosis. We concluded that an antioxidant should first be targeted and incorporated into human LDL. Second, the candidate compound should possess high bioavailability. The rationale and strategy for the analytical procedures are discussed in this report.