Despite the growing interest in amphiphilic block copolymers for their application in micelles as ideal drug delivery carriers, there remain some challenges related to biocompatibility, stability, degradability, and loading efficiency of the micelles. Herein, we report a novel hydrophobic, pH-responsive epoxide monomer, tetrahydropyranyl glycidyl ether (TGE). Anionic ring-opening polymerization affords the controlled synthesis of a series of its homopolymers (PTGE) and amphiphilic polymers, poly(ethylene glycol)-block-poly(tetrahydropyranyl glycidyl ether) (PEG-b-PTGE). Interestingly, these block copolymers with cyclic TGE moieties showed superior stability in biological media, high loading capacity, tunable release, and controllable degradation compared to the block copolymers with its acyclic analogue, 1-ethoxyethyl glycidyl ether (EEGE), widely employed in polyether, which satisfy all the required design principles and address the challenges in drug delivery systems. The superior biocompatibility coupled with the high stability of the novel functional epoxide monomer is anticipated to lead to the development of a versatile platform for smart drug delivery systems.