Pathogenic bacteria remain the primary health concern even after developing a broad spectrum of antibiotics. The emergence of drug-resistant strains increased mortality, perhaps resulting in a never-ending future pandemic. The researchers are currently concentrating their efforts on nanotechnology-based therapies to counteract resistance. The present review focuses on the antimicrobial characteristics of plant-mediated gold nanoparticles (Au NPs). First, the methodology and importance of green synthesis are highlighted. Variability in NPs characterization methods was identified, with dynamic light scattering, zeta potential, and thermogravimetric analysis limited to a few investigations. Second, the Au NPs synthesized using different plant extracts were found to be broad-spectrum antimicrobial agents against Pseudomonas aeruginosa, Escherichia coli, Cryptococcus neoformans, Candida glabrata, Aspergillus niger, etc. The lowest minimum inhibitory concentrations range (1.95–15.62 µg/mL) was observed with Au NPs synthesized using Thymus vulgaris extract against Staphylococcus aureus, P. aeruginosa, Bacillus subtilis, and E. coli. The effect was more pronounced with smaller NPs (<10 nm). The activity of Au NPs might be mediated through a two-way attack which includes nanoparticles’ diverse mechanisms like reactive oxygen species generation, etc., and surface-attached phytocompounds such as flavonoids, alkaloids, phenolics, terpenoids, tannins, etc. The futuristic role of nanotechnology-based interventions in managing microbial infections is imperative. Synergistic interactions of Au NPs with antibiotics, toxicity profiling, stability, and bioavailability could be major areas of NPs research.