The invention discloses a preparation method of chitosan-based medicine-carrying flexible sponge. The method comprises the following steps: taking chitosan as raw material, dropwisely adding a precipitant sodium hydroxide to obtain chitosan gel precipitate in the process of continuously stirring an acetic acid solution of chitosan, centrifugally cleaning the chitosan gel precipitate, and then mixing the chitosan gel precipitate with a cross-linking agent of oxidizing carboxymethyl cellulose, a plasticizer glycerol and an antibacterial drug tetracycline hydrochloride, and freeze-drying the castfilm to obtain the medicine-carrying flexible sponge body. According to the invention, the chitosan gel precipitate prepared by acid-base titration is used for preparing the sponge body, and the stability of the sponge obtained by freeze-drying is good, and the structure is not damaged when swelling is caused, and one-step molding is carried out, and the structure collapse caused by alkali washing and secondary freeze-drying is avoided, and because of the one-step molding, the chitosan-based medicine-carrying flexible sponge is convenient to carry medicine. According to the invention, glycerol is added as a plasticizer, so that the sponge is soft and elastic. The method has the advantages of short process period, simple and convenient process, low cost and suitability for commercial production.