Charge-convertible polymers are a class of intelligent polymers that can convert their charges in response to a certain stimulus in their environment. This unique property endows charge-convertible polymer-based biomaterials with great advantages in the treatment of disease. Drug-loaded charge-convertible polymeric nanoparticles have the ability to target tumor cells by converting their surface charges from negative or neutral to positive at the tumor site. In addition, charge-convertible polymeric biomaterials can form complexes with negatively charged therapeutic agents and release them through charge conversion at the desired time and site. In this review, the properties of charge-convertible polymers and their applications in the treatment of cancer and stroke are covered. More importantly, the limitations and perspectives of charge-convertible polymeric biomaterials in future clinical applications are discussed.