This research paper explores the field of nanobiotechnology, focusing on the design, characterisation, and potential dermal applications of metal oxide nanoparticles (MONPs). ZnO and FeO NPs exhibit distinctive properties that are valuable in dermato‐cosmetic applications and transdermal drug delivery. This study investigates Cannabidiol (CBD) as a capping agent for MONPs synthesis. Employing microwave‐assisted techniques, MONPs were synthesised using either CBD or polyvinylpyrrolidone (PVP) as capping agents. The TEM, SEM, FTIR, and XRD characterisation results confirmed the successful formation of CBD‐capped ZnO and FeO NPs exhibiting an average particle size of 90 and 76 nm, respectively. The cytotoxicity of CBD‐capped MONPs was evaluated on HaCaT cells over a concentration range of 100 to 6.25 μg/mL, which revealed that CBD‐capped ZnO NPs exerted a cytotoxic effect on HaCaT cells (IC50 85.34±1.17 μg/mL). In contrast, CBD‐capped FeO NPs and PVP‐capped MONPs exhibited negligible cytotoxicity (IC50 >100 μg/mL). TEM analysis revealed a noticeable structural alteration of ZnO NPs in the supplemented cell culture medium, which could contribute to enhanced NP uptake, thereby explaining the more pronounced cytotoxic effect of ZnO NPs. Therefore, the disparity in cytotoxic responses can be attributed to the protein coating adhering to the NPs surface in a biological medium.