Background: The reliance on medicinal plants is prevalent in many developing countries, including Ghana, where traditional herbal medicine forms a crucial component of healthcare. However, understanding the knowledge and practices related to the safety profiles of these commonly used medicinal plants remains limited. Objective: This study aimed to assess the knowledge and practice of patients regarding the safety profiles of medicinal plants at the Walewale Municipal Hospital in Ghana and to explore the relationship between sociodemographic factors and these variables. Methods: A total of 500 patients were interviewed using structured questionnaires. The sociodemographic characteristics, practice of medicinal plant use, and knowledge of safety profiles were evaluated. Chi-square analyses were conducted to determine associations between sociodemographic factors and the various practices and knowledge levels regarding medicinal plants. Results: The study revealed that 99.8% of respondents had used medicinal plants, with 76.6% indicating high usage for treating ailments. Despite this high prevalence, knowledge regarding safety profiles was alarmingly low; 36.0% of participants had low knowledge, while only 5.6% demonstrated a high understanding of safety issues. Significant correlations were found between knowledge and practice with respect to age (p = 0.00), gender (p = 0.00), education (p = 0.00), and occupation (p = 0.00), but no significant association with marital status (p = 0.96; p=0.6, respectively). Conclusion: The findings indicate a high level of practice regarding the use of medicinal plants among patients in Walewale, yet a concerning lack of knowledge about their safety profiles. This underscores the need for targeted educational initiatives to empower patients with proper information, ensuring safer integration of herbal therapies within conventional healthcare frameworks.