The invention provides wine taking shaddocks as a main raw material and a preparation method of the wine and relates to the technical field of fruit wine. The wine is prepared from raw materials in parts by weight as follows: 100-200 parts of shaddocks, 20-30 parts of baijiu, 5-10 parts of grapes, 5-10 parts of apples, 5-10 parts of Ya pears, 1-2 parts of honey, 4-7 parts of fructus lycii, 4-6 parts of radix astragali, 3-5 parts of radix angelicae sinensis, 6-8 parts of fructus momordicae, 1-2 parts of radix glycyrrhizae, 3-5 parts of red jujubes, 3-5 parts of lily bulbs, 2-3 parts of dry pectinase powder, 1-2 parts of cellulase, 15-20 parts of sucrose syrup, 5-7 parts of citric acid, 1-2 parts of yeast and 3-5 parts of a clarifying agent. The preparation method comprises the six steps of juice preparation, enzyme treatment, pre-fermentation, preparation of a traditional Chinese medicine extraction liquid, aging as well as filtration and sterilization. The wine takes the shaddocks as the main raw material, has the effects of relieving cough, reducing sputum, regulating qi, resolving lump, moistening the lung, clearing bowels, strengthening the spleen and stomach, removing alcohol poison and helping digestion, is clear and transparent, has no suspended matter and precipitates, has a good flavor, tastes good, is long in service life and meets the requirements of vast consumers.