Background. A risk factor associated with stroke onset is chronic kidney disease (CKD). To prevent stroke reoccurrence, it is necessary to strictly manage blood pressure, lipids, and plasma glucose. Therefore, some cases are forced to polypharmacy, elderly patients in particular. Polypharmacy often leads to adverse drug reactions and has the potential to negatively affect the rehabilitation of stroke patients. The aim of the present study was to investigate the effects of polypharmacy using a functional independence measure (FIM). Methods. A total of 144 stroke patients with CKD were included in the present analysis. We divided stroke patients into those taking six or more drugs (polypharmacy group) and those taking less than six drugs (nonpolypharmacy group) upon admission. Patient background features, laboratory data, and FIM scores were compared. Results. FIM-Motor (FIM-M) efficiency, age, and diabetes mellitus were positively associated with polypharmacy. FIM-M efficiency in the polypharmacy group was significantly lower than in the nonpolypharmacy group. Conclusion. Polypharmacy interferes with the effect of rehabilitation in stroke patients with CKD. Pharmacists and doctors should make efforts to optimize medications to be able to respond to the outcome of each patient.