Erythrocytes are responsible for delivering oxygen throughout the body. They have become suitable drug carriers due to outstanding advantages, such as a long lifespan in circulation, high biosafety, and low immunogenicity. Although erythrocyte-based drug delivery has good application prospects and has become a research hotspot in related fields, the application of erythrocyte-based drug delivery systems is rare in the clinic now. In this review, we discuss the characteristics of erythrocytes, diverse drug-loading approaches, and research progress of erythrocyte-based drug delivery systems. Finally, we explore the challenges of erythrocyte-based drug delivery in clinical application.