To achieve hydrophilic modification of poly(ε-caprolactone) (PCL), a series of amphiphilic copolymers, poly(ε-caprolactone)-b-poly(N,N-dimethylaminoethyl methacrylate-co-sulfobetaine methacrylate) (PCDSs), were synthesized with varying sulfobetaine compositions using a three-step synthetic strategy. Firstly, the hydroxyl-terminated polymer, PDMAEMA-OH was synthesized through free radical polymerization using AIBN as an initiator and 2-mercaptoethanol as a chain transfer agent. Subsequently, the block copolymer poly(ε-caprolactone)-b- poly(N,N-dimethylamino ethylmethacrylate) (PCD) was prepared through ring-opening polymerization of PDMAEMA-OH and ε-caprolactone employing Sn(OCt)2 as the catalyst. Finally, zwitterionization of the tertiary amine groups in PCD was achieved by treating it with 1,3-propane sultone (1,3-PS) in THF to obtain the desired PCDSs copolymers. The chemical compositions and the structures of PCDSs were confirmed by 1H nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). Additionally, self-assembly behavior in water was systematically investigated for both PCD and PCDSs copolymers. The results showed that these copolymers could form stable, pH-responsive micelles with diameters less than 150 nm via solvent evaporation method while also exhibiting efficient loading and release capabilities for the anti-tumor drug doxorubicin (DOX). Furthermore, cytotoxicity assay revealed low cell cytotoxicity of PCDS micelles towards L929, HeLa, and MCF-7 cells; however DOX-loaded PCDS micelles (PCDS/DOX), particularly those composed of 47% sulfobetaine content exhibited significant inhibitory effects on HeLa and MCF-7 cells along with enhanced cellular uptake efficiency. These findings highlight that pH-responsive zwitterionic sulfobetaine-based polymeric micelles derived from the PCDSs hold great promise for effective DOX delivery.