The temperature/pH dual-responsive gel spheres were prepared by orthogonal experiments and response surface methodology, and finally, the optimal synthesis conditions were obtained by a composite score, including swelling, mechanical properties, mass transfer properties, and so forth. The results showed that a sodium alginate concentration of 3% (w/v), CaCl2 concentration of 2% (w/v), gelling time of 40 h, drop height of 14 cm, NaCl concentration of 0.6% (w/v), N-isopropylacrylamide concentration of 0.03% (w/v), and acrylic acid concentration of 4.06% (w/v) were optimal synthesis conditions. The environmental change tolerance experiments showed that the nitrogen removal of the dual-response nitrifying gel spheres was better than the domesticated sludge at low temperatures (4 °C) and in alkaline (pH 9 and 10) conditions. The as-obtained gel spheres can respond intelligently to the changes in ambient temperature and pH. It is hoped that this study will provide technical parameters for the development and application of microbial immobilization carriers.