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Background & Objective: Nanoparticles are used in cosmetic and dermatologic products, due to better skin penetration properties. Incorporation of natural products exhibiting medicinal properties in nano-preparations could significantly improve the efficacy of these products and improve the quality of life without the side effects of synthetic formulations. Methods: We here report the green synthesis of Copper Oxide nanoparticles, using Cucumber extract, and their detailed bio-physical and bio-chemical characterization. Results: These Copper Oxide-Cucumber nanoparticles exhibit significant anti-bacterial and anti-fungal properties, Ultra Violet-radiation protection ability and reactive-oxygen species inhibition properties. Importantly, these nanoparticles do not exhibit significant cellular toxicity and, when incorporated in skin cream, exhibit skin rejuvenating properties. Conclusion: Our findings have implications for nanoparticle-based cosmetics and dermatologic applications.