Agitation is common in the early recovery period following traumatic brain injury (TBI), known as post-traumatic amnesia (PTA). Non-pharmacological interventions are frequently used to manage agitation, yet their efficacy is largely unknown. This systematic review aims to synthesize current evidence on the effectiveness of non-pharmacological interventions for agitation during PTA in adults with TBI. Key databases searched included MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO and CENTRAL, with additional online reviewing of key journals and clinical trial registries to identify published or unpublished studies up to May 2020. Eligible studies included participants aged 16 years and older, showing agitated behaviours during PTA. Any non-pharmacological interventions for reducing agitation were considered, with any comparator accepted. Eligible studies were critically appraised for methodological quality using Joanna Briggs Institute Critical Appraisal Instruments and findings were reported in narrative form. Twelve studies were included in the review: two randomized cross-over trials, three quasi-experimental studies, four cases series and three case reports. Non-pharmacological interventions were music therapy, behavioural strategies and environmental modifications, physical restraints and electroconvulsive therapy. Key methodological concerns included absence of a control group, a lack of formalised agitation measurement and inconsistent concomitant use of pharmacology. Interventions involving music therapy had the highest level of evidence, although study quality was generally low to moderate. Further research is needed to evaluate non-pharmacological interventions for reducing agitation during PTA after TBI.Systematic review registration number: PROSPERO (CRD42020186802), registered May 2020.