BACKGROUND: Polypharmacy is common amongst older people with dementia or mild cognitive impairment (MCI), increasing the risk of medication-related harm. Medicine optimisation and deprescribing to reduce polypharmacy is considered feasible, safe and can lead to improved health. However, for those living with dementia or MCI, this can be challenging. This systematic review aimed to summarise the evidence on the outcomes of medicine optimisation and deprescribing interventions for older people with dementia or MCI. METHODS: Literature was searched using CINAHL, Embase, Medline, PsychINFO, Web of Science and the Cochrane Library from database inception to January 2024. Papers reporting data specific to people with dementia or MCI from medicine optimisation and deprescribing interventional research studies of any design and in any setting were included. A narrative synthesis was conducted owing to heterogeneity of study designs and outcomes. Quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: A total of 32 papers reporting on 28 studies were included, with samples ranging from 29 to 17,933 patients and a mean patient age ranging from 74 to 88 years. Of the studies, 60% were undertaken in long-term care settings. Involvement of patients and/or carers in interventions was limited. Papers were grouped as either incorporating a medication review component (n = 13), education component (n = 5) or both (n = 14). Studies primarily focussed on medication-related outcomes, generally showing a positive effect on decreasing the number and improving appropriateness of medications. Fewer papers reported clinical outcomes (behavioural and psychological symptoms of dementia, falls, quality of life and cognition) with mixed findings. A reduction or no change in mortality or hospital attendance demonstrated safety of the interventions in the few papers reporting these outcomes. The quality of the evidence was mixed. CONCLUSIONS: Medicine optimisation and deprescribing interventions generally reduced the number and increased the appropriateness of medications, and although less frequently reported, these interventions seemed to be safe and showed an absence of worsening of clinical outcomes. This review highlights a need for further research, particularly in people with dementia or MCI living at home, with more focus on clinical outcomes and a greater involvement of patients and informal carers. PROTOCOL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42023398139].