The purpose of this study was to develop a poly(galacturonic acid) (PGA)-based hydrogel using a short-chain hyaluronate (sHA) cross-linker for medical applications. PGA was grafted with adipic acid dihydrazide (ADH) to yield PGA–ADH, an amine-containing PGA derivative. This PGA–ADH formed a water-insoluble hydrogel by reacting with 1,1'-carbonyldiimidazole (CDI)–grafted sHA (sHA–CDI) in aqueous solution. The sHA–cross-linked PGA hydrogel has a water content of about 94%–97% and compressive modulus of 10.7–26.9 kPa. The in vitro data indicated that the sHA–cross-linked PGA hydrogel is degradable and noncytotoxic, thus suitable for biomedical applications. Animal implant studies showed that the sHA–cross-linked PGA hydrogel membrane exhibited antiadhesion potency, significantly higher than that found in untreated rats and has great potential for future clinical applications.