The use of antibiotics has been an epoch-making invention in the past few decades for the treatment of infectious diseases. However, the intravenous injection of antibiotics lacking responsiveness and targeting properties has led to low drug utilization and high cytotoxicity. More importantly, it has also caused the development and spread of drug-resistant bacteria due to repeated medication and increased dosage. The differences in the microenvironments of the bacterial infection sites and normal tissues, such as lower pH, high expression of some special enzymes, hydrogen peroxide and released toxins, etc., are usually used for targeted and controlled drug delivery. In addition, bacterial surface charges, antigens and the surface structures of bacterial cell walls are all different from normal tissue cells. Based on the special bacterial infection microenvironments and bacteria surface properties, a series of drug delivery systems has been constructed for highly efficient drug release. This review summarizes the recent progress in targeted and responsive drug delivery systems for enhanced antibacterial properties.