BACKGROUND: There is uncertainty about the most appropriate ways to manage non-respiratory sleep disturbances in children with neurodisabilities (NDs). OBJECTIVE: To assess the clinical effectiveness and safety of NHS-relevant pharmacological and non-pharmacological interventions to manage sleep disturbance in children and young people with NDs, who have non-respiratory sleep disturbance. DATA SOURCES: Sixteen databases, including The Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE, were searched up to February 2017, and grey literature searches and hand-searches were conducted. REVIEW METHODS: For pharmacological interventions, only randomised controlled trials (RCTs) were included. For non-pharmacological interventions, RCTs, non-randomised controlled studies and before-and-after studies were included. Data were extracted and quality assessed by two researchers. Meta-analysis and narrative synthesis were undertaken. Data on parents' and children's experiences of receiving a sleep disturbance intervention were collated into themes and reported narratively. RESULTS: Thirty-nine studies were included. Sample sizes ranged from 5 to 244 participants. Thirteen RCTs evaluated oral melatonin. Twenty-six studies (12 RCTs and 14 before-and-after studies) evaluated non-pharmacological interventions, including comprehensive parent-directed tailored ( LIMITATIONS: Planned subgroup analysis was possible in only a small number of melatonin trials. CONCLUSIONS: There is some evidence of benefit for melatonin compared with placebo, but the degree of benefit is uncertain. There are various types of non-pharmacological interventions for managing sleep disturbance; however, clinical and methodological heterogeneity, few RCTs, a lack of standardised outcome measures and risk of bias means that it is not possible to draw conclusions with regard to their effectiveness. Future work should include the development of a core outcome, further evaluation of the clinical effectiveness and cost-effectiveness of pharmacological and non-pharmacological interventions and research exploring the prevention of, and methods for identifying, sleep disturbance. Research mapping current practices and exploring families' understanding of sleep disturbance and their experiences of obtaining help may facilitate service provision development. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016034067. FUNDING: The National Institute for Health Research Health Technology Assessment programme.