The prevalence of multi-drug resistant bacteria has increased significantly in recent years and becoming a significant threat to world health. This issue is greatly aggravated by the incorrect prescribing and excessive use of antibiotics. The rapid development of nanoscience and nanotechnology in the recent era has resulted in the emergence of various antimicrobial nanomaterials like Graphene, Graphene Oxide (GO), and Reduced Graphene Oxide (rGO). Due to their exceptional qualities, which include large surface areas and distinctive thermal, electrical, and physicomechanical properties, graphene oxide has lately been proven as an effective antimicrobials. Graphene oxide and reduced Graphene oxide unveiled toxicity to both Gram-positive and Gram-negative bacteria. Through the production of reactive oxygen species (ROS), physical destruction, chemical oxidation, and effects on the cell membrane and cell wall of microbes, GO causes microbial mortality and reduces microbial resistance. Three possible antimicrobial mechanisms of Graphene have been proposed: (i) inducing cellular damage with sharp edges of the nanomaterial; (ii) oxidative stress caused by the generation of superoxides with the treatment of Graphene nanomaterials; and (iii) wrapping the bacteria, and limiting physical movements and metabolism of bacteria. The combination of nanoparticles (NPs) and GO offers excellent potential in antimicrobial therapy and aids in overcoming antimicrobial resistance.