The invention relates to an oyster and kudzu root natural anti-alcohol agent and a preparation method thereof. The method comprises the following steps: (1) adding water in oyster, crushing and homogenizing, adjusting pH value of slurry, carrying out enzymolysis, refrigerating and centrifuging hydrolysate after the completion of enzymolysis to obtain supernatant, and spray-drying or freeze-drying in vacuum to obtain oyster extract powder; (2) grinding kudzu root, adding water, leaching in constant-temperature water bath, carrying out rough filtration to obtain leaching liquor, leaching residue again, filtering to obtain filtrate, merging the filtrate obtained for two times, adding amylase in the filtrate, stirring, placing in the constant-temperature water bath, carrying out enzyme inactivation using boiling water, carrying out multiple centrifugation to obtain light yellow kudzu root extracting solution, and spray-drying or freeze-drying to obtain kudzu root extract powder; and (3) mixing the oyster extract powder with the kudzu root extract powder in propart to obtain the oyster and kudzu root natural anti-alcohol agent. The raw materials of the method are very wide in sources and rich in nutrition, can protect liver, calm the nerves and clear away heat and toxic materials, are easy to be absorbed by the body without toxic or side effects and with high safety, and can be prepared into products in multiple forms.