African medicinal formulations, rooted in centuries of ethnomedical knowledge and biodiversity, represent a treasure trove of therapeutic agents with promising applications for promoting health and longevity. Whereas some are underutilized, natural products rich in bioactive phytoconstituents and promising medicinal bioresources contribute to antioxidant, anti-inflammatory, adaptogenic, neuroprotective, and anti-aging properties. These play roles in wellness and longevity through mechanisms involving redox modulation, cellular stress responses, and mitochondrial function, which align with emerging paradigms in geroscience. Using an integrative approach that combines ethnobotanical documentation, phytochemical profiling, and preclinical evaluation in models of metabolic dysfunction, immunosenescence, and neurodegeneration, evidence support the role of many African medicinal formulations in extending healthspan. Furthermore, we highlight the possibility of synergistic interactions among plant constituents (polyherbal formulations) and animal bioresources and the relevance of traditional preparation methods, such as prolonged decoction, fermentation, and pounded admixtures, and addition of edible mineral-ladden clays in enhancing bioavailability and efficacy. While noting the challenges associated with standardization, quality control, and safety assessment, there are opportunities for translational research through omics technologies, artificial intelligence-driven screening, and biotechnological enhancement that tripartite collaboration among indigenous practitioners, academic researchers and the biotechnology industry can drive. Importantly, sociocultural frameworks sustain traditional medicine practices, however there is a need for a model that will harmonize indigenous knowledge with modern drug development pipelines. African medicinal formulations are a viable and underexplored component of global strategies for preventive healthcare and healthy aging. They warrant recognition, preservation, and scientific validation as Africa’s medicinal heritage.