Traditional cancer therapy methods, especially those directed against specific intracellular targets or signaling pathways, are not powerful enough to overcome tumor heterogeneity and therapeutic resistance. Oncolytic peptides that can induce membrane lysis-mediated cancer cell death and subsequent anticancer immune responses, has provided a new paradigm for cancer therapy. However, the clinical application of oncolytic peptides is always limited by some factors such as unsatisfactory bio-distribution, poor stability, and off-target toxicity. To overcome these limitations, oncolytic polymers stand out as prospective therapeutic materials owing to their high stability, chemical versatility, and scalable production capacity, which has the potential to drive a revolution in cancer treatment. This review provides an overview of the mechanism and structure-activity relationship of oncolytic peptides. Then the oncolytic peptides-mediated combination therapy and the nano-delivery strategies for oncolytic peptides are summarized. Emphatically, the current research progress of oncolytic polymers has been highlighted. Lastly, the challenges and prospects in the development of oncolytic polymers are discussed.