<p>Diabetes mellitus (DM) is a growing public health concern that is affecting a significant proportion of older adults aged ≥ 65 years. Diabetes-related complications often lead to other comorbidities necessitating the use of multiple medications. Consequently, polypharmacy, defined as the concurrent use of five or more medications, is highly prevalent among older adults with DM. While sometimes necessary, greater medication counts increase the risk of medication nonadherence, potentially inappropriate medication use, drug-drug interactions, and adverse drug reactions. Thus, polypharmacy is considered a significant clinical challenge that also contributes to other geriatric syndromes such as falls, delirium, dementia, frailty, and functional decline, leading to increased healthcare utilization, hospitalization, and mortality. Older adults with DM are also heterogeneous, with two main groups, namely, sarcopenic-obesity (low muscle mass, high visceral adiposity, and high insulin resistance) and anorexic-malnourished (low nutritional intake and proneness to hypoglycemia), each patient requiring distinct therapeutic priorities and strategies. This review summarizes the prevalence, causes, and consequences of polypharmacy in older adults with DM, and outlines management strategies centered on comprehensive geriatric assessment.</p>