In the search for new metal-based anticancer agents as effective candidates for cisplatin, a lot of strategies such as synthesis of cisplatin analogs, trans-platinum compounds and non-platinum metal complexes have been put forward in the last forty years. The concept of multinuclearity for improving the chemotherapeutic activity has been proven in multinuclear platinum complexes such as BBR3464, recently, the effective approach has been successfully transferred to ruthenium complexes. In this review, we highlighted the recent progress in multinuclear platinum complexes and ruthenium complexes as anticancer agents, and their novel DNA binding properties such as phosphate clamps, long range DNA cross links, bisintercalation, interduplex cross links and DNA-protein cross-links were summarized to shed light on the rational design of polynuclear complexes as anticancer agents.