BACKGROUND: Multiple sclerosis (MS) is the most common neurological disease in young adults. Virtual reality (VR) offers a promising rehabilitation tool by providing controllable, personalised environments for safe, adaptable and engaging training. Virtual reality can be tailored to patients' motor and cognitive skills, enhancing motivation through exciting scenarios and feedback. OBJECTIVES: Primary objective To assess the effects of virtual reality interventions compared with an alternative or no intervention on lower limb and gait function, and balance and postural control in people with MS. Secondary objective To assess the effects of virtual reality interventions compared with an alternative or no intervention on upper limb function, cognitive function, fatigue, global motor function, activity limitation, participation restriction and quality of life, and adverse events in people with MS. SEARCH METHODS: We identified relevant articles through electronic searches of CENTRAL, MEDLINE, Embase, PEDro, CINAHL and Scopus. We also searched trials registries (ClinicalTrials.gov and the WHO ICTRP search portal) and checked reference lists. We carried out all searches up until August 2022. SELECTION CRITERIA: We included only (quasi-)randomised controlled trials (RCTs) that assessed virtual reality interventions, defined as "an artificial, computer-generated simulation or creation of a real-life environment or situation allowing the user to navigate through and interact with", in people with MS. The primary outcomes were lower limb and gait function, and balance and postural control. Secondary outcome measures were upper limb function, cognitive function, fatigue, global motor function, activity limitation, participation and quality of life, and adverse events. Eligible participants were people with MS who were 18 years or older. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the studies based on pre-specified criteria, extracted study data and assessed the risk of bias of the included studies. We used the risk of bias 2 tool (RoB 2). A third review author was consulted to resolve conflicts. MAIN RESULTS: We included 33 RCTs with 1294 people with MS. The sample sizes of the included studies were relatively small and there was considerable heterogeneity between studies regarding the virtual reality devices and the outcome measures used. The control group either received no intervention, conventional therapy or an alternative intervention (an intervention that does not fit the description of conventional therapy for the rehabilitation of people with MS). We most frequently judged the risk of bias as 'some concerns' across domains, leading to an overall high risk of bias in the majority of included studies for all outcome measures. Primary outcomes When compared with no intervention, virtual reality interventions may result in no difference in lower limb and gait function (Timed Up and Go, mean difference (MD) -0.43 sec, 95% confidence interval (CI) -0.85 to 0.00; 6 studies, 264 participants; low-certainty evidence) or balance and postural control (Berg Balance Scale, MD 0.29 points, 95% CI -0.1 to 0.68; 4 studies, 137 participants; very low-certainty evidence). When virtual reality interventions are compared to conventional therapy, results for lower limb and gait function probably do not differ between interventions (Timed Up and Go, MD -0.2 sec, -1.65 to 1.25; 4 studies, 107 participants; moderate-certainty evidence). However, virtual reality interventions probably improve balance and postural control (Berg Balance Scale, MD 2.39 points, 95% CI 1.22 to 3.57; 7 studies, 201 participants; moderate-certainty evidence), almost reaching the clinically important difference (3 points). Secondary outcomes Compared to no intervention, the use of virtual reality may also improve upper limb function (9-Hole Peg Test, MD -4.19 sec, 95% CI -5.86 to -2.52; 2 studies, 84 participants; low-certainty evidence), almost reaching the clinically important difference (4.38 points) and participation and quality of life, but the evidence is very uncertain (MS International QoL, MD 9.24 points, 95% CI 5.76 to 12.73; 2 studies, 82 participants; very low-certainty evidence). Compared to conventional therapy, virtual reality interventions may improve participation and quality of life (Falls Efficacy Scale-1, MD -3.07 points, 95% CI -5.99 to -0.15; 3 studies, 101 participants; low-certainty evidence), but not upper limb function (9-Hole Peg Test, MD 0.10 sec, 95% CI -1.70 to 1.89; 3 studies, 93 participants; low-certainty evidence). For other key secondary outcome measures, i.e. global motor function and adverse events, there were no data available as these were not measured in the studies. AUTHORS' CONCLUSIONS: We found evidence that the use of virtual reality may be more effective than no intervention in improving upper limb function and participation and quality of life. Training with virtual reality may be superior to conventional therapy for improving balance and postural control, and participation and quality of life. For the other outcomes, there was no clear difference between virtual reality and conventional therapy. There was insufficient evidence to reach conclusions about the effect of virtual reality on global motor function, activity limitations and adverse events. Additional high-quality, large-scale studies are needed to expand and confirm these findings.