Background <p>Antimicrobial resistance (AMR) is one of the most devastating health problems worldwide, many different approaches were tested to find the best alternative to conventional antimicrobial agents. The antifungal and antiviral activities of metal (silver) and metal oxide (ZnO and MgO) nanoparticles (Nps) were investigated against standard strains and clinical isolates.</p> Methodology <p>Chemical reduction method was used for synthesis of nanoparticles; the prepared nanoparticles were tested for their potential antifungal activity using two-fold microdilution technique and their antiviral activity using plaque assay. The cytotoxic effect near MIC values was evaluated using MTT assay on HepG2 cell line.</p> Results <p>Minimum inhibitory concentration (MIC) values from microdilution experiment were 0.5 and 1 mg.ml⁻¹ for Ag Nps and msAg Nps respectively, whereas ZnO Nps and MgO Nps showed MIC value of 500, and 1000 mg.ml⁻¹, respectively. A synergistic effect with N acetyl cysteine (NAC) was observed, reducing MIC values by up to 20-fold and about 20% reduction of their cytotoxic effect. Moreover, metal Nps showed antibiofilm activity and interference with membrane integrity of <i>C. albicans.</i> Nps also showed promising results as antiviral when tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and adenovirus. The antiviral activities were also augmented when Nps were combined with NAC; as the percentage difference in plaque formation was reduced up to 18%.</p> Conclusion <p>In essence, Nps are promising antimicrobial agents against fungal and viral infection with low cytotoxicity. The antimicrobial effect could be substantially improved when Nps are combined with the antioxidant NAC.</p>