Applying gel-type solid chlorine dioxide for the sustained release of chlorine dioxide has several shortcomings, such as no resistance to acid and alkali corrosion and poor mechanical properties. However, introducing quaternary ammonium, carboxyl, and amino groups into the hydrogel system can enhance its acid and alkali resistance. In this study, the effects of concentration of dry heat-modified starch, quaternized carboxymethyl cellulose, and chitin on the swelling behavior and mechanical properties of starch-based acid- and alkali-resistant hydrogels are investigated. The feasibility of the actual and predicted values of the tentative results is verified based on the response surface design to determine the optimal concentration ratio of acid- and alkali-resistant hydrogels. The results reveal that optimized process parameters are reliable. The maximum swelling ratio and compressive stress of the hydrogel are 5358.00% and 44.45 kPa, respectively, and its swelling behavior conforms to the pseudo second-order kinetic model. Thus, the present study can provide a new method of developing efficient starch-based chlorine dioxide hydrogels for the sustained release of chlorine dioxide.