Various Catharanthus species have long been valued in traditional medicinal systems across various cultures, notably in African Traditional Medicine and Indian Ayurveda. These plants are widely utilized for their therapeutic properties, with preparations made from different parts—such as leaves, roots, and the whole plant—being used in diverse forms including infusions, pastes, and extracts. Traditional healers employs Catharanthus plant-based remedies to address a wide range of health conditions. These include infectious diseases, immune system disorders, hormonal imbalances, metabolic dysfunctions, cardiovascular and neurological issues, respiratory ailments, and reproductive health concerns. The breadth of applications highlights the plant’s significance in holistic and integrative medicine practices. Among the different species, C. roseus and C. pusilla hold particular importance due to their potent medicinal value in the treatment of cancer and diabetes. The plant contains several bioactive alkaloids, such as vincristine and vinblastine, which are well known for their anticancer properties and are used in modern chemotherapy. Additionally, traditional formulations have shown benefits in managing blood sugar levels, making the species a valuable resource for diabetes care. The widespread use and enduring relevance of Catharanthus species in traditional medicine underscore their importance not only in cultural heritage but also in modern pharmacological research. These plants serve as a bridge between traditional knowledge systems and contemporary therapeutic development, warranting further scientific exploration and validation. In this chapter, associated traditional knowledge and applications of various Catharanthus species are presented.