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The widespread use of antibiotics has made the problem of bacterial resistance increasingly serious, and the study of new drug-resistant bacteria has become the main direction of antibacterial drug research. Among antibiotics, the fully synthetic oxazolidinone antibacterial drugs linezolid and tedizolid have been successfully marketed and have achieved good clinical treatment effects. Oxazolidinone antibacterial drugs have good pharmacokinetic and pharmacodynamic characteristics and unique antibacterial mechanisms, and resistant bacteria are sensitive to them. This Perspective focuses on reviewing oxazolidinones based on the structural modification of linezolid and new potential oxazolidinone drugs in the past 10 years, mainly describing their structure, antibacterial activity, safety, druggability, and so on, and discusses their structure–activity relationships, providing insight into the reasonable design of safer …