Background Delirium is a common acute neurocognitive disorder. Despite evidence-based delirium guidelines recommending antipsychotic use be avoided, these medications are commonly used to manage delirium symptoms, even though they carry significant risks. Synthesised evidence regarding the effectiveness of interventions to support clinicians to minimise antipsychotic use is lacking. Objectives To describe and report on the effectiveness of interventions targeting antipsychotic use for delirium management in adults in hospital or residential aged care. Methods Systematic literature search of MEDLINE, Embase, CINAHL, PsycINFO, Web of Science and the Cochrane Library. Two reviewers independently screened studies, extracted data, and appraised quality. A narrative synthesis of findings was generated. Results Fourteen studies from nine countries, using RCT (n=4), cohort (n=3), and quasi-experimental (n=7) designs, were included. Sample sizes were small (range 25 – 320). Multicomponent interventions (n=4) focused on antipsychotic discontinuation (n=2) and a mix of education, environmental adaptations and non-pharmacological strategies for care (n=2). Single-component interventions were either non-pharmacological (n=5) (rocking chair, music, audio-visual projections, complementary therapy, exercise), or pharmacological (n=3) (Dexmedetomidine, Ramelton, insulin). One small study (n = 57) of audio-visual projections reported a significant (p=.004) reduction in antipsychotic use. Non-significant reductions in antipsychotic use were reported in two studies of multi-component interventions. Conclusion The absence of high-quality evidence on effective single- or multi-component interventions for avoiding antipsychotic use leaves clinicians without the guidance and strategies needed to provide care that aligns with the Australian Delirium Standard. Significant investment in research, education, and resources is needed to advance the quality and safety of delirium care.