The number of fatalities caused by multidrug-resistant (MDR) bacteria is over 700,000 annually due to widespread antibiotic usage. So, there is a need of new antibiotics, materials that work like antibiotics, or combinations of antibiotics with nanomaterials that could help in treating the infections which is caused by MDR bacteria. The present study describes the synthesis of ZnO nanoflakes using a co-precipitation method. The ZnO nanoflakes and ZnO nanoflakes combinations with carbapenem antibiotics were tested against carbapenem-resistant (CR) clinical isolates. The SEM analysis showed surface morphology of the synthesized nanoflakes-like structure of ZnO. All 67 CR isolates were tested and showed inhibitory action at varying concentrations of ZnO nanoflakes. ZnO nanoflakes were found to have an inhibitory effect against Escherichia coli and Klebsiella pneumoniae at lowest concentration of 1.25 mg.ml^-1 of ZnO NPs with average zone size (mean ±SD) 1.91±2.94 mm and 2.00±4.14 mm and the average zone size of ZnO nanoflakes against Acinetobacter baumanni and Pseudomonas aeruginosa was 9.89±0.76 mm and 10.17±0.39 mm at 2.5 mg.ml^-1 concentration. The combined action of ZnO nanoflakes with Meropenem 10 mcg demonstrated synergetic activity against CR pathogens, with an average zone of inhibition measuring 15.2 mm in diameter. ZnO nanoflakes illustrated considerable antibacterial activity against MBL-producing gram-negative clinical isolates at the lowest concentration. Chemically synthesized ZnO nanoflakes may offer a superior future expectation as a nano-antibiotic to treat the infection caused by CRE bacteria.