Many medicines have anticholinergic properties, which have previously been correlated with a range of adverse effects, including cognitive impairment, hallucinations and delirium. These effects are potentially of concern for people with dementia. This systematic review investigated the effect of anticholinergic medicines on the health outcomes of people with pre-existing dementia. Embase, Medline and the Cochrane Library were searched from January 2000 to January 2021. Studies were included if they matched the following criteria: (1) the intervention involved anticholinergic medications; (2) the study was conducted in people with pre-existing dementia; (3) there was at least one comparator group; and (4) the outcome of interest was clinically measurable. A total of 14 studies met the inclusion criteria. Most studies used an anticholinergic burden scale to measure anticholinergic exposure. Five high-quality studies consistently identified a strong association between anticholinergic medications and all-cause mortality. Anticholinergics were also found to be associated with longer hospital length of stay in three studies. Inconsistent findings were reported for cognitive function (in 4 studies) and neuropsychiatric functions (in 2 studies). In single studies, anticholinergic medications were associated with the composite outcome of stroke and mortality, pneumonia, delirium, poor physical performance, reduced health-related quality of life and treatment modifications due to reduced treatment response or symptom exacerbation. While the evidence suggests that anticholinergic medication use for people with dementia has a strong association with all-cause mortality, the association with cognitive and other clinical outcomes remains uncertain. Hence, further studies are needed to substantiate the evidence for other outcomes.