Gold nanoparticles have gained popularity as an effective drug delivery vehicle due to their unique features. In fact, antibiotics transported via gold nanoparticles have significantly enhanced their potency in the recent past. The present study used an approach to synthesize gold nanoparticles in one step with the help of cefoxitin antibiotic as a reducing and stabilizing agent. Cefoxitin is a second-generation cephalosporin that loses its potential due to modification in the porins (ompK35 and ompK36) of Gram-negative pathogens. Thus, the present study has developed an idea to revive the potential of cefoxitin against clinical Gram-negative pathogens, i.e., Escherichia coli and Klebsiella pneumoniae, via applying gold nanoparticles as a delivery tool. Prior to antibacterial activity, characterization of cefoxitin–gold nanoparticles was performed via UV–visible spectrophotometry, dynamic light scattering, and electron microscopy. A characteristic UV–visible scan peak for gold nanoparticles was observed at 518 nm,  potential was estimated as 􀀀23.6  1.6, and TEM estimated the size in the range of 2–12 nm. Moreover, cefoxitin loading efficiency on gold nanoparticles was calculated to be 71.92%. The antibacterial assay revealed that cefoxitin, after loading onto the gold nanoparticles, become potent against cefoxitin-resistant E. coli and K. pneumoniae, and their MIC50 values were estimated as 1.5 g/mL and 2.5 g/mL, respectively. Here, gold nanoparticles effectively deliver cefoxitin to the resistant pathogens, and convert it from unresponsive to a potent antibiotic. However, to obtain some convincing conclusions on the human relevance, their fate and toxicity need to be evaluated.