Malaria kills millions of people annually, and it is one of the major causes of preventable mortality in the world. Of the different plasmodium species that induce malaria, Plasmodium falciparum and Plasmodium vivax account for the most severe form of malarial disease in humans. This review focuses on understanding preventive measures, mutation-based disease evolution, malaria-related biomarkers, and potential plant bioactive components for the treatment and management of malaria. The burden of malaria drug resistance has made it necessary for scientists to focus on alternative therapeutics, with particular interests in those involving plant-based bioactive components that could mediate biochemical pathways, consisting of metabolic interactions essential for parasitic inhibition. To avoid artefacts or false positives, these bioactive components from plant sources are further filtered using the "pan-assay-interfering compounds" (PAINS) tool. This review discussed the history of malaria treatment, current treatment options, malaria preventive measures, and challenges associated with current treatment strategies. Additionally, this work discusses the barriers while developing drugs from phytochemicals and the steps needed to accelerate the development of new antimalarial from the lead compounds.