The invention relates to a dexamethasone small-molecular hydrogel drug delivery system and a preparation method thereof. According to the invention, dexamethasone is subjected to derivatization by using 1,4-succinic anhydride or glutaric anhydride, such that a dexamethasone prodrug is formed. Through pH value regulation, the prodrug is subjected to auto-hydrolysis, such that dexamethasone drug molecules are released; the molecules are subjected to self-assembly spontaneously, such that the small-molecular hydrogel is formed. Specifically, dexamethasone 21 hydroxyl site derivatization is achieved by using 1,4-succinic anhydride (glutaric anhydride), such that gel-forming precursor molecules are obtained. The precursor molecules have good solubility, high drug load, and simple components. Through auto-hydrolysis, dexamethasone drug molecules can be released, and can be spontaneously self-assembled into the hydrogel. The process does not need to be driven by any chemical reagent. According to the system, drug molecules and derivatized drug are adopted as carriers, such that other carriers are not needed. Therefore, the dexamethasone novel delivery system provided by the invention assists in improving solubility and drug load of dexamethasone in water, and is potential to be developed into a novel preparation form of dexamethasone.