Three cysteine derivatives were synthesized in high yield by ligating monomethoxy oligo(ethylene glycol) (OEG) to L-cysteine thiol group using sulfenyl chlorides. These OEG groups containing di-, tri-, and tetra-EG units were linked with L-cysteine via disulfide bond. The three monomers were then converted into corresponding N-carboxyanhydrides (NCAs) using triphosgene in THF. Subsequent ring-opening polymerization (ROP) of disulfide bond containing NCAs gave three poly-EG(x)-L-cysteine derivatives. The obtained poly-EG(x)-L-cysteine with x = 3 and 4 displayed thermal-responsive behaviors in water, but the temperature-induced phase transition was found surprisingly irreversible. Such irreversible thermal-responsive behaviors were attributed to cross-linking arising from disulfide bonds exchanges. Using PEG-NH2 as macroinitiator, we also prepared two PEG-b-poly-EG(x)-L-cysteine diblocks, which could undergo irreversible thermal-induced sol gel transition, which was caused by the disulfide bonds exchanging reactions. These hydrogels displayed partially shear-thinning and rapid recovery properties allowing new capabilities to construct stimuli-responsive injectable hydrogels in biomedical applications.