Prescribing medications is a fundamental practice in the management of illnesses that necessitates in-depth knowledge of clinical pharmacology. Polypharmacy, or the concurrent use of multiple medications by individuals with complex health conditions, poses significant challenges, including an increased risk of drug interactions and adverse reactions. The Saudi Vision 2030 prioritises enhancing healthcare quality and safety, including addressing polypharmacy. Artificial intelligence (AI) offers promising tools to optimise medication plans, predict adverse drug reactions and ensure drug safety. This review explores AI’s potential to revolutionise polypharmacy management in Saudi Arabia, highlighting practical applications, challenges and the path forward for the integration of AI solutions into healthcare practices.