Background: Youth with cerebral palsy do not have enjoyable, accessible, and scalable exercise options that can empower them to independently maintain their cardiometabolic health. Objective: The primary aim is to examine the preliminary efficacy of a 12-week home-based virtual reality tele-exergaming intervention on several indicators of cardiometabolic health in youth with cerebral palsy compared to the wait list control. A secondary aim is to describe feasibility metrics, namely, recruitment, retention, and adherence rates; perceived enjoyment; intervention safety; and management issues. The tertiary aim is to generate a theory that reveals critical behavioral mechanisms of adherence to tele-exergaming. Methods: In this parallel group design randomized controlled trial, 34 inactive youths with cerebral palsy are randomly allocated to one of two groups: a group that immediately receives 12 weeks of virtual reality exergaming with tele-physical education or a wait list control group that undergoes their habitual activity for 12 weeks. Participants are recruited from a Children's Hospital and community network. At baseline (week 0), week 6, and week 12, high sensitivity C-reactive protein and blood insulin, hemoglobin A1c, triglycerides, cholesterol, and pressure are measured by the youth and a caregiver at home using a blood spot test kit and blood pressure cuff. They will also self-measure their lung function and body weight using a peak flow meter and bathroom scale, respectively. Collections are supervised by research staff via videoconference. Changes in outcomes are compared between and within groups using exploratory statistical analyses and descriptive statistics. At postintervention or dropout, participants will undergo semistructured interviews to identify behavioral mechanisms that underly participation. Results: Recruitment procedures started in June 2022. All data are expected to be collected by October 2023. Full trial results are expected to be published by February 2024. Secondary analyses of data will be subsequently published. Conclusions: This trial tests an innovative serious exergaming virtual reality program that includes a completely remote enrollment, assessment, and intervention tele-protocol. The knowledge obtained will inform the development of a larger effectiveness trial for improving the health and well-being of youth with cerebral palsy.