The invention discloses a biocompatible hyper-dispersant preparation method, and belongs to the technical field of hyper-dispersant preparation. The preparation method comprises: carrying out mixed water bath heating on glycerol, sucrose and the like, vacuumizing, carrying out a thermal insulation reaction, adding epichlorohydrin in a dropwise manner, carrying out a water bath reaction, filtering to obtain a filtrate, mixing with a citric acid solution, filtering to obtain a filtrate, concentrating to obtain a modified base liquid, carrying out oil bath heating on the modified base liquid, epsilon-caprolactone and the like, filtering to obtain a filtrate, and standing to obtain the biocompatible hyper-dispersant. According to the present invention, the preparation steps are simple, the obtained product has advantages of good biocompatibility, high dispersion stability, safety, environmental protection and no toxicity, and the protection layer does not generate the thinning phenomenon under the acidic condition.