The invention relates to a preparation method of egg yolk immunoglobulin for preventing and curing mouth diseases, and a safe toothpaste with the egg yolk immunoglobulin as main material. When preparing the IgY, according to a main pathogen causing the decayed tooth, periodontal disease and halitosis, types of main pathogenic bacteria are cultured in a conventional method. A complex antigen is made with the cultured strains and injected to laying poultries (including hens, ducks, and turkeys and so on). And then needed IgY is made by the yolks of immune eggs laid by the poultries. When making the toothpaste with the IgY, the toothpaste comprises 0.01-10.0% egg yolk immunoglobulin, vesicant and other components. The IgY activity is maintained and the effect is strengthened by adopting gentle vesicant, film microcapsule, sandwich type or interlayer type toothpaste tube and oral mucosa adsorbent. The prepared toothpaste without harmful chemicals has great effect on preventing and curing decayed tooth, periodontal disease and halitosis, and can be swallowed.