Introduction: Currency notes harbor and transmit infectious microorganisms if handled without proper care. Hence, in this study, silver nanoparticles biosynthesized from autochthonous S. aureus OS (S-AgNPs) isolated from Nigeria currency notes (Naira) were used to assess the antimicrobial activity of S-AgNPs against the pathogenic money microbiome and to determine their protective effect on coated currency notes. Methods: Naira notes (15) each, were randomly collected from poultry product sellers, food vendors, fish, sellers, and shopkeepers in Ondo City, Nigeria. A molecular tool was used for the identification of bacterial isolates using 16S ribosomal RNA gene sequences. Staphylococcus aureus-silver nanoparticles (S-AgNps) were characterized by UV‒visible spectroscopy. The antibacterial and antifungal activities of the biosynthesized S-AgNPs against isolated microorganisms were determined using the agar well diffusion method. Results: A total of one hundred and twenty (120) S-AgNP-coated and non-coated papers were improvised as currency notes and randomly distributed among preinformed business owners. The highest bacterial count of 7.90 cfu/mL was recovered from Naira notes collected from food vendors. The highest fungal count of 4.70 cfu/mL on the Naira note was collected from poultry product sellers. S. aureus had the highest frequency of 29.60%. At 5.0 µg/mL, the S-AgNPs had the greatest inhibitory effects (17.30 mm) on Streptococcus pyogenes and Rhizopus stolonifer. The provided currency notes coated with the biosynthesized S-AgNPs showed no growth of microorganisms. Biosynthesized S-AgNPs showed pronounced antimicrobial potential against pathogenic microorganisms isolated from currency (Naira notes). Conclusion: AgNPs can be used as coating agents during currency production to minimize the spread of disease-causing pathogenic microorganisms.