Increasing resistance to carbapenem antibiotics has become a particular concern. Combination therapy might constitute an effective way to control drug-resistant bacterial infections. Here, we show that AuRh nanoparticles (NPs) have a synergistic antibacterial effect with a small-molecule antibiotic (imipenem), and they exhibit excellent antibacterial efficacies by increasing intracellular reactive oxygen species levels and enhancing the permeability of the bacterial membrane. In particular, the combination therapy restores the efficacy of imipenem against carbapenem-resistant Klebsiella pneumoniae (CRKP), with a 128-fold reduction in the minimum inhibitory concentration. In the treatment of lung infections, the combination of AuRh NPs (2 mg kg−1) and imipenem (2 mg kg−1) more effectively inhibits CRKP infection, with a 50% increase in the survival rate of mice compared with groups treated with imipenem or AuRh NPs alone. For in vitro and in vivo safety studies, AuRh NPs combined with imipenem show no significant toxicity, even at an injected concentration of 100 mg kg−1 in mice. This combination therapeutic provides an effective treatment for drug-resistant bacterial infections.