The invention discloses a composition for resisting duck plague, freeze-dried powder, and a preparation method and use of the freeze-dried powder, and belongs to the technical field of veterinary feed additives. The composition comprises, by weight, 90-100 parts of a duck plague-resistant yolk antibody and 0.5-2 parts of a duck plague-resistant transfer factor. The freeze-dried powder comprises, by weight, 95-97 parts of the duck plague-resistant yolk antibody, 1-2 parts of the duck plague-resistant transfer factor, 0.2-0.3 parts of an inactivator, 0.01-0.02 parts of an antiseptic and 2.05-3.6 parts of a heat-resistant freeze-dried protective agent, and has the advantages of low preservation conditions, long preservation time, high antibody titer and good biological activity. Through combined use of the duck plague-resistant yolk antibody and the duck plague-resistant transfer factor, the freeze-dried powder has effects of preventing and treating duck plague, improves duck immunity and survival rate, is convenient for use and has a low cost.