The European population is ageing. Food Supplements (FSs) are foods with particular characteristics, consumed by elderly people for various purposes, including combating nutritional deficits. Their consumption in this age group, associated with a high prevalence of polypharmacy, can enhance interactions. Potential drug-food (or food supplements), drug-drug interactions and polypharmacy are common health issues among older adults. The prevalence of polypharmacy is high, and preliminary data also indicate that there is significant FS use, increasing the risk of the duplication of therapies and various adverse reactions as well as drug-FS and FS-FS interactions. Therefore, the intervention of health professionals in mitigating these risks is essential. This review highlights and discusses the association between FSs, polypharmacy, and adverse reactions due to the risk of potential interactions between these products. Moreover, it also provides current scientific evidence regarding the use of FSs by the elderly. A review of the challenges, advantages, and risks of using FSs in elderly people who are malnourished and/or polymedicated, focusing on the good practises needed to support healthy ageing, is presented. In this regard, this paper aims to help health professionals better deal with the issue of the use of multiple FSs and polypharmacy, overcome the malnutrition problem, and improve the health and well-being of older adults.