Polypharmacy, defined as the concurrent use of five or more medications, is an increasing concern, particularly among older adults and individuals with multiple health conditions. It significantly heightens the risk of medication-related harm, adverse drug reactions (ADRs), prescribing errors and hospitalisations. Ageing alters drug pharmacokinetics and pharmacodynamics, rendering older individuals especially vulnerable. Polypharmacy has substantial effects on oral health. A primary issue is xerostomia and salivary gland hypofunction, often caused by medications with anticholinergic, sympathomimetic or diuretic properties. The cumulative effects of multiple medications taken together can severely diminish salivary flow, raising the risk of dental caries, oral candidosis, mucositis, ulceration and dysphagia. An increased risk of bleeding is another significant consequence, especially with combined antiplatelet and anticoagulant therapies (e.g. aspirin, clopidogrel, warfarin and direct oral anticoagulants [DOACs]), sometimes compounded by over-the-counter (OTC) products. This complicates dental procedures that require haemostasis and manifests in the oral cavity with various signs, including petechiae, purpura and ecchymosis. Furthermore, polypharmacy elevates the risk of medication-related osteonecrosis of the jaw (MRONJ). While antiresorptive (e.g. bisphosphonates and denosumab) and antiangiogenic therapies carry individual risk, concurrent use, especially alongside chemotherapy, steroids or disease-modifying antirheumatic drugs (DMARDs), significantly amplifies the likelihood and severity of MRONJ, particularly following dental extractions or trauma. Careful medication review and management are crucial to mitigate these oral health complications associated with polypharmacy.