Incorporating multiple pyridyl disulfide (PDS) moieties into polymer chains allows the fabrication of a chemically cross-linked hydrogel through the rapid thiol–disulfide exchange reaction. By aminolysis in the presence of 2,2′-dithiodipyridine (DTP), the end groups of polymers synthesized via reversible addition−fragmentation chain transfer (RAFT) polymerization can readily be converted into PDS-groups. In this contribution, a RAFT-synthesized graft copolymer with thermoresponsive poly[di(ethylene glycol) methyl ether methacrylate] forming the backbone and hydrophilic poly(N,N-dimethylacrylamide) as the side chains is presented. The copolymer chains exhibit surprisingly a two-step lower critical solution temperature transition in aqueous solutions. After modification of the end groups of the backbone and side chains, the PDS-terminated chains can react with a dithiol cross-linker to form a thermoresponsive hydrogel. In a reducing environment, the cleavable disulfide linkages lead to on-demand dissolution of the hydrogel. The resulting thiol-terminated chains undergo a reversible sol–gel transition in response to redox variations, expanding the potential application areas of such a polymer system.