BackgroundNight shift work-related disturbed biological rhythm and insufficient sleep affect the functioning of brain activity and thus impair cognitive performance and mood state, which potentially leads to negative and even devastating results for both individuals and patients. A virtual reality (VR)-based restorative environment has shown to be an effective new technique to reduce stress and improve cognitive performance, but little is known about its mechanism of improving neuronal activity and connectivity.MethodsThis is a randomized, controlled, single-center clinical trial. A total of 140 medical staff will be enrolled and randomized in a 1:1 allocation to either the VR immersion group (intervention group) or the control group. In the morning after the night shift, the participants in the intervention group will watch 360° panoramic videos of immersive VR natural restorative environments for 10 min, while the participants in the control group will just rest for 10 min. Assessments of abbreviated Profile of Mood States Questionnaire (POMS) and verbal fluency task (VFT) performances, as well as oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) and total hemoglobin concentration acquired by functional near-infrared spectroscopy (fNIRS) will be performed at baseline (day work), the morning after night shift but before the intervention (previous) and after intervention (post). Data collected after a night shift will be compared to baseline performance as well as between the two groups.DiscussionThis trial will investigate the effects of the night shift and VR-based restorative environment intervention on mood, cognitive performance, and neuronal activity and connectivity. A positive result in this trial could encourage hospitals to apply VR technology to reduce physical and mental dysfunction during of night shifts among medical staff in every department. Furthermore, the findings from this study will contribute to understanding the underlying neuromodulation mechanisms of how restorative environments influence mood and cognition.Trial registrationChinese Clinical Trial RegistryChiCTR2200064769. Registered on 17 October 2022.