BackgroundThe beneficial effects of gardening as a form of physical activity have garnered growing interest in recent years. Existing research suggests that physical activity enhances brain function through modifying synaptic plasticity, growth factor synthesis, and neurogenesis. Gardening physical activity is a promising, cost-effective, non-invasive intervention that can easily be augmented in the rehabilitation of neurodegenerative conditions. However, there is still insufficient literature. This protocol describes a systematic review to be conducted of scientific literature on the benefits of gardening as a physical activity that can promote neuroplasticity and improve cognitive function. This information can be useful as an intervention for persons who experience cognitive impairment brought on by cancer and chemotherapy in developing countries such as South Africa where there is real need to access cognitive rehabilitation.Methods and analysisThe systematic review strategy will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. An electronic literature database search of MEDLINE (PubMed), Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science will be carried out using medical search terms (MeSH), with English as the only permitted language, during the time period of January 2010 to December 2022. We will search for and review studies on how gardening as a physical activity impacts neuroplasticity and cognition. Two reviewers will read the titles, and abstracts and full text of the studies identified during the search to exclude records that do not meet the inclusion criteria. Data will then be extracted from the remaining studies. Any differences in opinion arising between the reviewers during the procedure will be resolved through discussion with a third reviewer. The Joanna Briggs Institute (JBI) Critical Appraisal Tool checklist will be utilized independently by two reviewers to evaluate the possibility of bias. The included articles will be subjected to narrative synthesis, with the results being presented in a thematic manner.Ethics and disseminationThere are no need for ethical approval because no patient data will be gathered. The results will be disseminated through an open-access peer-reviewed indexed journal, presented scientific meetings.PROSPERO registration number: CRD42023394493