Leukocytes play a vital role in immune responses, including defending against invasive pathogens, reconstructing impaired tissue, and maintaining immune homeostasis. When the immune system is activated in vivo, leukocytes accomplish a series of orderly and complex regulatory processes, which are essential in the occurrence and control of diseases. While cancer and inflammation-related diseases like sepsis are critical medical issues that require urgent settlement plaguing humankind around the world, leukocytes have been shown to largely gather at the focal site and significantly contribute to inflammation and cancer progression. Therefore, the living leukocyte-based drug delivery systems have attracted considerable attention in recent years due to the innate and specific targeting effect, low immunogenicity, improved therapeutic efficacy, and low reverse effect. In this review, we introduce the recent advances in the development of living leukocyte-based drug delivery systems including macrophage, neutrophil, and lymphocyte as promising treatment strategies for cancer and inflammation-related diseases (e.g., immunotherapy, chemotherapy, and photodynamic therapy). We also discuss the advantages, current challenges, and limitations of the living leukocyte-based drug delivery systems, as well as provide our perspectives on the future development of precision and targeted therapy in the clinic. Collectively, we expect that such kind of living cell-based drug delivery system is promising to improve or even revolutionize the treatments of cancers and inflammation-related diseases in the clinic . This article is protected by copyright. All rights reserved.