In order to overcome the significant side effects and the acquired resistance of platinum-based anticancer drugs, great efforts have been devoted to designing new platinum compounds or non-platinum transition metal anticancer complexes with improved pharmacological properties and a broader range of antitumor activity. Among them, the new complexes based on natural alkaloid and their derivatives provide a novel approach to potential (pro-)drugs. This review was mainly focused on the recent progresses of alkaloid-metal based anticancer agents, including metal complexes of natural or synthetic alkaloids, liriodenine, β-carboline, and quinolinoline as anticancer agents, their in vitro anticancer activities and primary action mechanism. Additionally, the future development of hybrid alkaloid and its derivatives metal complexes as anticancer drugs was discussed, which might hold a promise for overcoming multidrug resistance (MDR).