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Background The traditional use of medicinal plants is an integral part of African culture and plays a major role in African societies. For centuries, plants have been used to cure diseases and till date, a vast majority of the African people especially in rural communities depend on the use of medicinal plants for the treatment of various ailments. Main body The Cucurbitaceae family has a diversity of medicinally relevant species which also play significant roles in food security in Africa. While some are underutilised and are sourced from the wild, others are domesticated and cultivated for food. This review therefore highlights the significance of Cucurbitaceae species in Eastern and Southern African countries. The use of various species in the traditional food and medicine systems of these countries is documented. The review further discusses some poisonous species with close resemblance to edible plants. The fatal effect of consuming any part of such plant species like young or old leaves and unripe fruit is highlighted. Conclusion This review is thus a documentation of the crucial role of Cucurbitaceae species in food security, treatment of a variety of diseases and its negative effect on humanity and livestock.