The invention provides a preparation method of protoporphyrin disodium, and belongs to the field of synthesis of organic compounds. The method comprises the following steps: ensuring that protoporphyrin, absolute methanol and concentrated sulfuric acid are subjected to alcohol acid reaction in an ultrasound condition, so as to obtain protoporphyrin diester; ensuring that the protoporphyrin diester, a NaOH methanol solution and methylbenzene are subjected to saponification reaction in an ultrasound condition, so as to obtain the protoporphyrin disodium. The method has the advantages that assistance of ultrasonic wave is adopted to replace high-temperature reflux, so as to form the protoporphyrin disodium, hydrogen chloride gas is not required to be prepared during preparation, the adoptionof strong-toxicity reagents, such as chloroform, is further avoided, a high-temperature condition is not required to be use, the technology is simplified, and the whole process is easy to operate.