IntroductionParkinson’s disease is one of the most common neurodegenerative diseases. Deep brain stimulation (DBS) can improve motor symptoms in patients with middle and late Parkinson’s disease, reduce the use of levodopa, and thus reduce drug-related side effects. Postoperative delirium can significantly reduce the short-term and long-term quality of life in elderly patients, which can be alleviated by dexmedetomidine (DEX). However, whether prophylactic DEX could reduce the incidence of postoperative delirium in patients with Parkinson’s disease was still unknown.Methods and analysisThis is a single-centre, randomised, double-blinded, placebo-controlled group trial. A total of 292 patients aged 60 years and above elected for DBS will be stratified according to DBS procedure, subthalamic nucleus or globus pallidus interna, then randomly allocated to the DEX group or the placebo control group with a 1:1 ratio, respectively. In the DEX group, patients will be injected with the DEX continuously with an electronic pump at a rate of 0.1 µg/kg/hour for 48 hours at the beginning of general anaesthesia induction. In the control group, normal saline will be administered at the same rate for patients as in the DEX group. The primary endpoint is the incidence of postoperative delirium within 5 days after surgery. Postoperative delirium is assessed by the combination of the Richmond Anxiety Scale and the Confusion Assessment Method (CAM) for the intensive care unit or the 3-minute diagnostic interview for CAM as applicable. The secondary endpoints include the incidence of adverse events and non-delirium complications, the length of stay in the intensive care unit and hospital and all-cause 30-day mortality after the operation.Ethics and disseminationThe protocol has been approved by the Ethics Committee of Beijing Tiantan Hospital of Capital Medical University (KY2022-003-03). The results of this study will be disseminated through presentation at scientific conferences and publication in scientific journals.Trial registration numberNCT05197439.