Introduction Ageing—along with its associated physiological and pathological changes—places individuals at a higher risk of multimorbidity and treatment-related complications. Today, polypharmacy, a common and important problem related to drug use, occurs subsequent to this multimorbidity in the elderly in all populations. In recent decades, several scientific investigations have studied polypharmacy and its correlates, using different approaches and definitions, and their results have been inconclusive. Differences in definitions and approaches in these studies form a barrier against reaching a conclusion regarding the risk factors and consequences of polypharmacy. It is therefore imperative to establish an appropriate definition of polypharmacy.

Methods and analysis A systematic review will be conducted using PubMed, Scopus, Web of Science, EMBASE, PsycINFO and AgeLine bibliographic databases, as well as the grey literature on polypharmacy in older adults to answer these two questions: What definitions in the literature are being used for polypharmacy in older people?, and Which definitions are more comprehensive and applicable? 2 independent reviewers will conduct the primary screening of the articles and data extraction, and eligible sources will be selected after discussing non-conformities. All extracted data from selected articles will be categorised based on the type of study participants, study design and setting, the methodological quality of primary studies and any other potential source of heterogeneity, and results will be summarised in a table, which will contain the levels of evidence and methodological quality of the included studies. The most comprehensive definition of polypharmacy will be selected from the final list of definitions through an international expert webinar.

Ethics and Dissemination This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal.