The invention relates to high-activity wild grape wine with seeds and a preparation method thereof. The preparation method comprises the steps of preprocessing wild grapes, carrying out split charging, aerobic fermentation and anaerobic fermentation, processing grape seeds, and carrying out post-fermentation, filtration, encapsulation, sealing and after-packaging. According to the high-activity wild grape wine, high-activity anti-oxidation nutrient substances such as resveratrol and organic acid are increased, meanwhile, a deep processing and utilizing scheme is provided for by-products produced during the brewing of grape wine from grape seeds and the like, and the raw material resources are well utilized. On this basis, the specific preparation technological process is detailed, the antioxidant activity of the product and the content contrast of relevant substances are verified by virtue of subsequent detection, and meanwhile, a sensory evaluation result is matched so as to determine an optimal preparation method. The content of active components in the product is increased, meanwhile, the optimal taste and flavor of the product are guaranteed, and the product has multiple superiorities of nutrition, health, delicacy, storage resistance, easiness in production and process and the like.