A novel oral delivery system consisting of thermoresponsive zwitterionic poly(sulfobetaine methacrylate) (PSBMA) and pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) is synthesized via free radical polymerization. This copolymer can self-aggregate into nanoparticles via electrostatic attraction between ammonium cation and sulfo-anion of PSBMA and successfully encapsulate anticancer drug, curcumin (CUR), with highest loading content of 2.6% in the P(SBMA-co-DPA) nanoparticles. The stimuli-responsive phase transition behaviors of P(SBMA-co-DPA) copolymers at different pH buffer solution show pH-dependent upper critical solution temperature (UCST) attributed to the influence of protonation/deprotonation of the pH-responsive DPA segments. Through the delicate adjustment of the PSBMA/PDPA molar ratios, the stimuli-responsive phase transition could be suitable for physiological environment. The kinetic drug release profiles demonstrate that P(SBMA-co-DPA) nanoparticles have the potential as oral delivery carriers due to their effective release of entrapped drugs in the stimulated intestinal fluid and preventing the deterioration of drug in stimulated gastric fluid.