Antibiotics play an irreplaceable role in the prevention and treatment of bacterial infection diseases. However, because of the improper use of antibiotics, bacterial resistance emerges as a major challenge of public health all over the world. The small thiol molecules such as glutathione can directly react and conjugate with some antibiotics, which thus contribute to drug susceptibility and resistance. Recently, accumulating evidence shows that there is a close link between the antibacterial activities of some antibiotics and reactive oxygen species (ROS). Thioredoxin and glutathione systems are two main cellular disulfide reductase systems maintaining cellular ROS level. Therefore, these two thiol-dependent antioxidant systems may affect the antibiotic susceptibility and resistance. Microorganisms are equipped with different thiol-dependent antioxidant systems, which make the role of thiol-dependent antioxidant systems in antibiotic susceptibility and resistance is different in various bacteria. Here we will focus on the review on the advances of the effects of thiol-dependent antioxidant system in the bacterial antibiotic susceptibility and resistance.