Biomolecules from plant extracts have gained significant interest in the synthesis of nanoparticles owing to their sustainable properties, cost efficiency, and environmental wellbeing. An eco-friendly and facile method has been developed to prepare Cu-Co-Ni trimetallic nanoparticles with simultaneous bio-reduction of Cu-Co-Ni metal precursors by aqueous extract of oregano (Origanum vulgare) leaves. Dramatic changes in physicochemical properties of trimetallic nanoparticles occur due to synergistic interactions between individual metal precursors, which in turn outclass the properties of corresponding monometallic nanoparticles in various aspects. The as biosynthesized Cu-Co-Ni trimetallic nanoparticles were initially analyzed using ultraviolet (UV)–visible spectroscopy. The morphology, structure, shape, and size of biosynthesized trimetallic nanoparticles were confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD) spectroscopy. The elemental analysis was carried out by energy-dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) microscopy was carried out to explain the critical role of the biomolecules in the Origanum vulgare leaf extract as capping and stabilizing agents in the nanoparticle formation. Additionally, simultaneous thermogravimetric analysis (TGA) and differential thermogravimetry (DTG) analysis was also performed to estimate the mass evaluation and rate of the material weight changes. The photocatalytic activity of as biosynthesized trimetallic nanoparticles was investigated towards methylene blue (MB) dye degradation and was found to be an efficient photocatalyst for dye degradation. Kinetic experiments have shown that photocatalytic degradation of MB dye followed pseudo-first-order kinetics. The mechanism of the photodegradation process of biogenic Cu-Co-Ni trimetallic nanoparticles was also addressed.