Antimicrobial resistance (AMR) remains an urgent and formidable challenge to global public health. Developing new medicines or alternative therapies to address AMR is imperative. Herein, we rationally designed and synthesized a series of Au(I)-based aggregation-induced emission luminogens (AIEgens) to combat drug-resistant bacterial infections. Through systematic screening, we identified an optimal AIEgen, called complex 5, which can rapidly discriminate between gram-positive (G) and gram-negative bacteria (G) bacteria, and exert robust and broad-spectrum antimicrobial potency against diverse drug-resistant bacterial strains, including those intractable to treat in clinic. Furthermore, extensive testing against a variety of clinical drug-resistant isolates, coupled with the successful treatment of methicillin-resistant Staphylococcus aureus-infected skin wounds unequivocally validates the high efficiency and broad-spectrum activity of complex 5. Therefore, complex 5 emerges as a promising candidate for combating drug-resistant bacterial infections in clinic, and this work provides inspiration for developing new solutions to address the escalating global challenge of AMR.