Bacteria infected cells acting as “Trojan horses” not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden intracellular bacteria, especially the multidrug-resistant (MDR) bacteria. Herein, aggregation-induced emission luminogens (AIEgens) such as TBPs showed potent broad-spectrum bactericidal activity against both extracellular and intracellular Gram-positive pathogens at low-dose levels. TBPs triggered reactive oxygen species (ROS)-mediated membrane damage to kill bacteria, regardless of light irradiation. Additionally, such AIEgens activated mitochondria dependent autophagy to eliminate intracellular bacteria in host cells. Compared to the routinely used vancomycin in clinics, TBPs showed comparable efficacy against methicillin-resistant Staphylococcus aureus (MRSA) in vivo. Our studies demonstrate that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.