The synthesis of a chemically cross-linked polymer hydrogel consisting exclusively of amino acids is described in this paper. A natural amino acid, aspartic acid was polymerized to polysuccinimide which was cross-linked by a tetrapeptide sequence designed for proteolytic degradation, and then the corresponding poly(aspartic acid) hydrogel was obtained by alkaline hydrolysis. The hydrogel dissolved in the presence of trypsin. According to in vitro cellular assays, the degradation products of the hydrogel cross-linked with the peptide were non-cytotoxic and non-cytostatic. The sustained release of an encapsulated macromolecular model drug, FITC-dextran, was triggered by the degradation of the hydrogel induced by trypsin. These results suggest the potential application of the trypsin-responsive hydrogel for drug delivery in the small intestine.