Since the discovery of ion-exchange resins, they have been used in many fields, including pharmacy. Ion-exchange resin-mediated preparations can realize a series of functions, such as taste masking and regulating release. However, it is very difficult to extract the drug completely from the drug–resin complex because of the specific combination of the drug and resin. In this study, methylphenidate hydrochloride extended-release chewable tablets compounded by methylphenidate hydrochloride and ion-exchange resin were selected for a drug extraction study. The efficiency of drug extraction by dissociating with the addition of counterions was found to be higher than other physical extraction methods. Then, the factors affecting the dissociation process were studied to completely extract the drug from the methylphenidate hydrochloride extended-release chewable tablets. Furthermore, the thermodynamic and kinetic study of the dissociation process showed that the dissociation process obeys the second-order kinetic process, and it is nonspontaneous, entropy-decreasing, and endothermic. Meanwhile, the reaction rate was confirmed by the Boyd model, and the film diffusion and matrix diffusion were both shown to be rate-limiting steps. In conclusion, this study aims to provide technological and theoretical support for establishing a quality assessment and control system of ion-exchange resin-mediated preparations, promoting the applications of ion-exchange resins in the field of drug preparation.