<p><i>Azadirachta indica</i> (neem) and <i>Hibiscus sabdariffa</i> (roselle) are medicinal plants with therapeutic properties. Drug-resistant bacterial and fungal species threaten public health. Nanoparticles (NPs) which are environmentally friendly have gained popularity for its low cost and mild toxicity. This study is aimed at evaluating the antimicrobial activity of plant-mediated NPs. The bacteria and fungus isolates obtained from a laboratory for further subjected to further microbiological analysis. Leaves of Neem and roselle were used to prepare plant extracts. Copper nanoparticles (CuNPs) were synthesized using the extract mixed with copper sulphate solution (CuSO₄), while zinc nanoparticles (ZnNPs) were formed by heating the extract with zinc nitrate (ZnNO₃). The NPs were characterized using Ultraviolet–Visible spectrophotometer and Fourier Transform Infrared Spectroscopy analysis. The in-vitro antimicrobial activity of ZnNP and CuNP was investigated against five isolates. The results revealed that neem contains the least amount of alkaloids, flavonoids, and phenol, while roselle has the highest concentration of tannins, saponins, terpenoids, steroids, and phenol. Antibiotics susceptibility results show resistance to <i>Staphylococcus aureus</i>, <i>Streptococcus pneumonia, Escherichia coli,</i> and <i>Pseudomonas aeruginosa</i>. The antimicrobial activity of CuSO₄ and ZnNO₃ showed the highest zone of inhibition in <i>Escherichia coli</i>, while the lowest in <i>Streptococcus pneumonia</i>. The absorbance spectrum showed inconsistent NP activities, with peaks at 400 and 1000&#xa0;nm. Copper and zinc concentrations in plant-based NPs and extracts were below WHO limits, indicating their safety. Therefore, plant-mediated copper and zinc nanoparticles offer a safe, low-toxicity alternative to conventional antimicrobial agents due to their chemical interactions and potential for biomedical and environmental applications.</p>