The present study investigates the green synthesis, characterization, and antibacterial evaluation of CuO–CeO₂ nanocomposites using Enicostemma littorale leaf extract as a natural reducing and stabilizing agent. Plant-mediated synthesis offers an eco-friendly and sustainable alternative to conventional chemical methods by eliminating the use of hazardous reagents and minimizing environmental impact. The phytochemical constituents present in E. littorale, including flavonoids, phenolics, alkaloids, and glycosides, facilitated the formation and stabilization of the mixed metal oxide nanocomposite. The synthesized CuO–CeO₂ nanocomposite was characterized using X-ray diffraction (XRD) and UV–visible spectroscopy to evaluate its structural and optical properties. XRD analysis confirmed the successful formation of a crystalline heterostructure comprising monoclinic CuO and fluorite-type CeO₂ phases without detectable impurity peaks. The average crystallite size, calculated using the Debye–Scherrer equation, was found to be in the range of 25–35 nm, indicating successful nanoscale synthesis. UV–visible spectroscopic analysis revealed a characteristic absorption peak at approximately 331 nm, corresponding to O²⁻→Cu²⁺ and O²⁻→Ce⁴⁺ charge-transfer transitions. The enhanced optical response and reduced band-gap characteristics suggest improved charge separation and photocatalytic potential arising from the synergistic interaction between CuO and CeO₂. The antibacterial activity of the synthesized nanocomposite was evaluated against both Gram-positive (Bacillus subtilis, Bacillus cereus, and Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae) bacterial strains using the agar well diffusion method. The nanocomposite exhibited significant antibacterial activity with inhibition zones ranging from 15 to 19 mm. The highest activity was observed against Staphylococcus aureus (19 mm), while notable inhibition was also recorded against Bacillus subtilis (18 mm), Bacillus cereus (17 mm), Klebsiella pneumoniae (17 mm), Pseudomonas aeruginosa (16 mm), and Escherichia coli (15 mm). The enhanced antimicrobial performance is attributed to reactive oxygen species generation, membrane disruption, and oxidative stress induced by the CuO–CeO₂ heterostructure. The findings demonstrate that E. littorale-mediated CuO–CeO₂ nanocomposites possess excellent crystallinity, desirable optical properties, and broad-spectrum antibacterial activity, highlighting their potential for applications in environmental remediation, antimicrobial coatings, water treatment, and biomedical technologies