Amina Jega Yusuf^1,2,3,4 , Abdulrahman Abubakar Usman¹, Celestina Oluranti Alebiosu¹, Mustapha Salihu¹, Kasimu Ghandi Ibrahim^5,6, Jamila Aminu⁷, Fatima Abdurrahman Galadanci^8,9,10, Lawal Hassan Gusau¹¹, Jiangnan Peng⁴

Abstract

Malaria remains a major global health challenge, with the continued emergence of antimalarial drug resistance underscoring the need for new, effective, and sustainable therapeutic strategies. Natural products have historically served as an important source of antimalarial agents, exemplified by quinine and artemisinin, and continue to provide structurally diverse bioactive compounds with significant therapeutic potential. This narrative review synthesizes current evidence on the role of natural products in antimalarial drug discovery, emphasizing the integration of ethnopharmacological knowledge with green chemistry principles to support sustainable drug development. A structured literature search was conducted across PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar to identify relevant mechanistic, ethnobotanical, and pharmacological studies. The review highlights the antiplasmodial activities of major classes of natural compounds, including terpenoids, alkaloids, flavonoids, quinones, and other secondary metabolites, together with their mechanisms of action, drug discovery pipelines, and emerging technologies such as green extraction methods, nanotechnology based delivery systems, and high-throughput screening. It also discusses the contribution of traditional medicinal knowledge to the identification of novel lead compounds and the importance of biodiversity conservation and equitable benefit-sharing. Despite persistent challenges related to standardization, bioavailability, pharmacokinetics, and clinical translation, natural products remain a promising foundation for the development of next-generation antimalarial therapies capable of addressing the growing burden of drug-resistant malaria through environmentally sustainable and culturally informed approaches.