In recent years, the green chemistry based-approach for the synthesis of nanoparticles has shown tremendous promise as an alternative to the costly and environmentally unfriendly chemically synthesized nanoparticles. In this study, copper oxide nanoparticles (CuO NPs) were synthesized through a green approach using the water extract of papaya (Carica papaya L.) peel biowaste as reducing as well as stabilizing agents, and copper (II) nitrate trihydrate salt as a precursor. The structural properties, crystallinity, purity, morphology, and the chemical composition of as-synthesized CuO NPs were analyzed using different analytical methods. The analytical results revealed that the synthesized CuO was observed as spherical-like in particles with measured sizes ranging from 85–140 nm and has monoclinic crystalline phase with good purity. The Fourier transform infrared (FTIR) spectroscopic results confirmed the formation of the Cu-O bond through the involvement of the potential functional groups of biomolecules in papaya peel extract. Regarding photocatalytic activity, the green-synthesized CuO NPs were employed as a photocatalyst for the degradation of palm oil mill effluent (POME) beneath the ultraviolet (UV) light and results showed 66% degradation of the POME was achieved after 3 h exposure to UV irradiation. The phytotoxicity experiment using mung bean (Vigna radiata L.) seed also showed a reduction of toxicity after photodegradation.