Polypharmacy in older adults is a significant health issue characterized by the use of multiple medications, often more than four chronic ones. It leads to increased healthcare costs, medication interactions, adverse drug reactions, non-adherence, falls, injuries, and reduced quality of life. In Iran, a growing older population with high illiteracy rates and limited healthcare access exacerbates the problem. Despite universal health coverage, poor public health service quality in health centers worsens polypharmacy management. Polypharmacy is prevalent globally, with rates ranging from 14.6% to 60.8% in Europe and 40% of U.S. adults over 65 taking 5-9 medications. In Iran, 36.9% of older adults experience polypharmacy, with many taking inappropriate medications. Risk factors include chronic diseases, geriatric syndromes, and factors like cognitive decline and poly-provider prescribing. Loneliness and lack of social support increase the risk of non-adherence. Recommendations include comprehensive medication reviews, patient education, technology use, and inter-professional collaboration. A multidisciplinary approach involving healthcare providers, patients, and caregivers is essential to optimize medication use and improve health outcomes. Addressing polypharmacy requires careful monitoring, deprescribing strategies, and tailored care for older adults, especially those living alone.Polypharmacy in older adults is a significant health issue characterized by the use of multiple medications, often more than four chronic ones. It leads to increased healthcare costs, medication interactions, adverse drug reactions, non-adherence, falls, injuries, and reduced quality of life. In Iran, a growing older population with high illiteracy rates and limited healthcare access exacerbates the problem. Despite universal health coverage, poor public health service quality in health centers worsens polypharmacy management. Polypharmacy is prevalent globally, with rates ranging from 14.6% to 60.8% in Europe and 40% of U.S. adults over 65 taking 5-9 medications. In Iran, 36.9% of older adults experience polypharmacy, with many taking inappropriate medications. Risk factors include chronic diseases, geriatric syndromes, and factors like cognitive decline and poly-provider prescribing. Loneliness and lack of social support increase the risk of non-adherence. Recommendations include comprehensive medication reviews, patient education, technology use, and inter-professional collaboration. A multidisciplinary approach involving healthcare providers, patients, and caregivers is essential to optimize medication use and improve health outcomes. Addressing polypharmacy requires careful monitoring, deprescribing strategies, and tailored care for older adults, especially those living alone.