Background: The selection of the maintenance of general anesthesia may affect the development of postoperative delirium (POD), notably for Parkinson’s disease (PD) patients, due to their lower cognitive reserve. The present study was designed to compare the potential impact of propofol vs. sevoflurane based general anesthesia maintenance methods on the development of POD in PD patients following deep brain stimulation (DBS) surgery. Methods: A total of 125 PD patients who were scheduled to undergo DBS surgery were randomly divided into the propofol (n = 63) and the sevoflurane groups (n = 62). The patients in the two groups randomly received propofol- or sevoflurane-based general anesthesia. The Confusion Assessment Method (CAM) was employed by an investigator who was blinded to the anesthesia regimen and was administered twice per day from postoperative day 1 until discharge. Results: The incidence of POD was 22.22% (14/63) with propofol anesthesia and 20.97% (13/62) with sevoflurane anesthesia (p = 0.865). In addition, no difference was noted in the duration and severity of delirium between the propofol and sevoflurane groups. Conclusions: In the present study, propofol- and sevoflurane-based general anesthesia exhibited comparable results with regard to the POD incidence in PD patients undergoing deep brain stimulation surgery.