Global population aging has led to a substantial increase in the number of older adults receiving long-term pharmacological treatment, often involving polypharmacy. Long-term medication use is often linked to negative oral health outcomes, such as xerostomia, periodontal disease, dental caries, and changes in the oral microbiome, even if it is necessary for treating systemic conditions. The general health, nutritional state, and quality of life of elderly people are all significantly impacted by these diseases. This narrative review integrates recent data on biological causes, genetic vulnerability, and public health consequences to investigate oral self-care as a preventive strategy in older persons on medication. The effects of long-term medication therapy on oral tissues, salivary function, inflammatory responses, and microbial balance are given special attention, as is the role of genetic variants linked to immunological and inflammatory pathways on individual variability. The review also evaluates oral self-care interventions aimed at reducing medication-related oral complications, such as the use of fluoride, mechanical plaque control measures, and caregiver-assisted oral care practices. Oral self-care is viewed from a public health perspective as a scalable and affordable strategy for reducing oral health disparities in older populations. The results highlight the significance of preventative, individualized, and integrated oral health interventions within larger healthcare frameworks for older persons taking long-term medications.