It is unclear whether virtual reality (VR)-based exercise can improve physical fitness in people with intellectual disability (ID). This systematic review therefore aimed to synthesize existing evidence regarding the efficacy of VR-based exercise on physical fitness in people with ID. Eligible articles were searched through six major electronic databases from inception until August 15, 2022. Returned studies were screened through predefined inclusion and exclusion criteria. Data from the included studies were then extracted and synthesized. A total of 13 randomized controlled trials were included and 12 of them were found to have good research quality. Different physical fitness outcomes were evaluated: (1) muscular fitness (d = 0.05-2.12; proportion of effect = 5/6), (2) cardiorespiratory fitness (d = 0.12-0.67; proportion of effect = 5/5), (3) flexibility (d = 0.81; proportion of effect = 1/2), (4) body composition (d = 0.10; proportion of effect = 2/3), (5) balance (d = 0.23-1.65; proportion of effect = 6/7), (6) coordination (d = 0.19-0.48; proportion of effect = 2/3), (7) speed and agility (d = 0.13-0.46; proportion of effect = 4/4), and (8) overall motor proficiency (d = 0.02-1.08; proportion of effect = 1/3). While there was some preliminary evidence showing that VR-based exercise could improve muscular fitness, cardiorespiratory fitness, balance, and speed and agility in individuals with ID, other outcomes showed less conclusive or limited positive evidence. Overall, additional studies are needed to understand the benefits of VR-based exercise on physical fitness in people with ID.