Abstract: A semaglutide soluble microneedle composition and a preparation method therefor are disclosed. The soluble microneedle composition comprises a needle material and a base material. The needle material comprises semaglutide and hyaluronidase, and a mass ratio of semaglutide to hyaluronidase is (0.05-172):1. The semaglutide and the hyaluronidase are combined to prepare the soluble microneedle composition, so that the semaglutide can be better promoted to diffuse into the systemic circulation. Compared with a semaglutide oral tablet, the soluble microneedle composition has the advantages that the blood sugar regulating effect is improved by nearly 40 times, the bioavailability of semaglutide is improved, and the dosage and the cost of the hypoglycemic drug are reduced. Moreover, the soluble microneedle technology causes no pain during use and reduces the discomforts of users.