The article reviews the research progress of disulfide bond-based drug delivery systems (DDS) targeting the tumor microenvironment. Disulfide bonds, due to their reductive responsiveness and ability to target high glutathione (GSH) levels in the tumor environment, have become a focus in recent years. The construction of reduction-sensitive nanomedicine delivery systems based on disulfide bonds has attracted significant attention. These systems can effectively target the tumor microenvironment, enhance drug release, and reduce side effects. The article discusses various drug loading strategies, carrier design, and the controlled release mechanisms of these DDS. It also explores the clinical applicability and challenges faced in the translation of disulfide bond-based DDS. Key aspects include the targeting conditions of the tumor microenvironment, such as GSH/ROS and pH, and the use of highly expressed ligands on tumor cell surfaces. The article highlights the advantages and disadvantages of different types of nanocarriers, such as polymeric nanoparticles, liposomes, and mesoporous silica nanoparticles, and their modifications to improve stability and targeting. Additionally, it details the connection modes of disulfide bonds in drug delivery systems, including drug-polymer, drug-drug, and polymer-polymer connections, and their applications in improving drug transport, loading, and synergistic effects. The article concludes by discussing multifunctional delivery carriers based on disulfide bonds, such as those used in photodynamic therapy, and their potential in enhancing therapeutic outcomes.The article reviews the research progress of disulfide bond-based drug delivery systems (DDS) targeting the tumor microenvironment. Disulfide bonds, due to their reductive responsiveness and ability to target high glutathione (GSH) levels in the tumor environment, have become a focus in recent years. The construction of reduction-sensitive nanomedicine delivery systems based on disulfide bonds has attracted significant attention. These systems can effectively target the tumor microenvironment, enhance drug release, and reduce side effects. The article discusses various drug loading strategies, carrier design, and the controlled release mechanisms of these DDS. It also explores the clinical applicability and challenges faced in the translation of disulfide bond-based DDS. Key aspects include the targeting conditions of the tumor microenvironment, such as GSH/ROS and pH, and the use of highly expressed ligands on tumor cell surfaces. The article highlights the advantages and disadvantages of different types of nanocarriers, such as polymeric nanoparticles, liposomes, and mesoporous silica nanoparticles, and their modifications to improve stability and targeting. Additionally, it details the connection modes of disulfide bonds in drug delivery systems, including drug-polymer, drug-drug, and polymer-polymer connections, and their applications in improving drug transport, loading, and synergistic effects. The article concludes by discussing multifunctional delivery carriers based on disulfide bonds, such as those used in photodynamic therapy, and their potential in enhancing therapeutic outcomes.