<p>This study presents the eco-friendly synthesis of copper-doped zinc oxide nanoparticles (Cu–ZnO NPs) using <i>Asystasia gangetica</i> leaf extracts as a reducing and stabilizing agent. To reveal their structural, morphological, and optical properties, the synthesized nanoparticles were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet-visible spectroscopy, and energy-dispersive X-ray spectroscopy. The dye degradation efficiency of Cu–ZnO NPs was evaluated for Rhodamine B dye under varying pH, nanoparticle concentration, dye concentration, and reaction time using response surface methodology. Statistical analysis using a central composite design showed that lower nanoparticle concentrations (50 ppm), higher dye concentrations (30 ppt), alkaline pH 9, and extended reaction times (120 min) resulted in optimal dye degradation. The ANOVA results, with a significant <i>F</i>-value and <i>R</i>² values indicating a good fit, confirmed the model’s adequacy. This green synthesis approach offers a sustainable method for nanoparticle production and its practical application in environmental remediation, particularly in the degradation of synthetic dyes. These findings contribute to the advancement of nanotechnology for eco-friendly applications, with potential implications for wastewater treatment and environmental sustainability.</p>