Polyaspartamide, derived from polysuccinimide (PSI), has the advantage of conveniently presenting desired functional groups by ring-opening addition of amine-based nucleophiles to the succinimidyl ring moieties of PSI. Using diamines with varying lengths of poly(ethylene glycol) linker, polyaspartamide presenting amine groups with controllable grafting density and length, namely, poly(2-hydroxyethyl aspartamide)-g-amino-poly(ethylene glycol) (PHEA-PEGAm) could be synthesized. This PHEA-PEGAm was then used to develop in situ forming hydrogels by Schiff base formation with aldehyde-containing alginate (Alg-ALD). By modulating the graft architecture (i.e., grafting length and density), the mechanical properties of the resulting Alg-PHEA hydrogels could be controlled in a broad range. Remarkably, the hydrogels were shown to undergo facile degradation and complete dissolution in physiological conditions, regardless of hydrogel mechanics, by the expedited hydrolysis through the action of remaining amine groups, which was also heavily influenced by the graft architecture. Moreover, the rate of degradation could be further controlled by additional ionic cross-linking of alginate. The potential application as an injectable drug delivery system was demonstrated by measuring drug release kinetics and monitoring degradation ex vivo.