Leukemia is a heterogeneous group of hematological malignancies distinguished by differentiation blockage and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow (BM) and peripheral blood (PB). There are various types of leukemia in which intensive chemotherapy regimens or hematopoietic stem cell transplantation (HSCT) are now the most common treatments associated with severe side effects and multi-drug resistance in leukemia cells. Therefore, it is crucial to develop novel therapeutic approaches with adequate therapeutic efficacy and selectively eliminate leukemic cells to improve the consequences of leukemia. Medicinal plants have been utilized for ages to treat multiple disorders due to their diverse bioactive compounds. Plant-derived products have been used as therapeutic medication to prevent and treat many types of cancer. Over the last two decades, 50 % of all anticancer drugs approved worldwide are from natural products and their derivatives. Therefore this study aims to review natural products such as polyphenols, alkaloids, terpenoids, nitrogen-containing, and organosulfur compounds as antileukemic agents. Current investigations have identified natural products efficiently destroy leukemia cells through diverse mechanisms of action by inhibiting proliferation, reactive oxygen species production, inducing cell cycle arrest, and apoptosis in both in vitro, in vivo, and clinical studies. Current investigations have identified natural products as suitable promising chemotherapeutic and chemopreventive agents. It played an essential role in drug development and emerged as a possible source of biologically active metabolites for therapeutic interventions, especially in leukemia. DATA AVAILABILITY: Data will be made available on request.