Malaria is considered one of the deadliest and widespread endemic diseases in Africa. This disease does not fit in the category of Neglected Tropical Diseases (NTDs) as described by the World Health Organization (WHO), although it shares characteristics with NTDs, such as prevalence in tropical and subtropical regions and primarily affecting impoverished communities, malaria has received significant global attention and funding. NTDs generally refer to diseases that have historically received less attention and fewer resources compared to major diseases like malaria, HIV/AIDS, and tuberculosis. Malaria infection is usually located in tropical and subtropical regions where the transfer of the causative parasite, Plasmodium malaria, occurs through an intermediate host, the female Anopheles mosquito. Resistance is the main problem facing the efforts to combat malaria where the parasite and/or the mosquito can now resist most of the chemical agents utilized in the disease control. African plants and their natural products possess a lot of interesting treatment options against malaria. Most of these African plants may carry promising lead compounds that may act as an effective anti-malarial agent shortly. This chapter focuses on the African medicinal plants together with their active ingredients with potential anti-malarial activity either against the parasite itself or the mosquito malaria vector. Twenty plant families together with certain genera and species belonging to such families were detailed in this chapter. The main active phytoconstituents involved in the anti-malarial activity were flavonoids, phenolic acids, triterpenoids, fatty acids, chlorins, naphthoquinones, lignans, coumarins, and others. The data summarized in this chapter was accessed through many scientific databases such as Scopus®, Web of Science®, Google Scholar®, and PubMed®.