Lotus seeds polyphenols have not been studied at the anti-oxidation activity in oil and the extraction by now. Microwave-assisted extraction was employed to extract polyphenols from lotus seeds, which is a process that uses microwave energy and solvents to extract target compounds from various matrices. Orthogonal analysis methodology was used to determine the optimal extraction conditions for microwave power, ethanol concentration, extraction time, and solid-liquid ratio which were 300 W, 90%, 35 s, and 1:10, respectively. Ethanol concentration is the most significant factor influencing on the yield of lotus seed polyphenols. Antioxidant trials using oil have shown lotus seed polyphenols can effectively inhibit the production of the peroxide and anisidine in oil to a certain extent, and these polyphenols have strong anti-oxidation activity. From anti-oxidation synergistic effect on oils with the lotus seed polyphenols and other antioxidants, vitamin C shows the strongest synergy.