In this study, ZnO nanoparticles with a size of 192 nm were produced via green synthesis using Diospyros kaki L. peel extract and were characterized by energy-dispersive X-ray analysis (EDAX), scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-Visible spectroscopy, dynamic light scattering (DLS), Brunauer-Emmett-Teller (BET), and zeta potential (ZP) analysis. The produced nanoparticles were tested for photocatalytic degradation of methylene blue and optimized using the Box-Behnken design. Under optimum conditions (pH: 10, dye concentration: 10 ppm and catalyst amount: 0.13 g and pH: 7, dye concentration: 10 ppm and catalyst amount: 0.6 g), 100% dye removal was achieved in 270 min and the model was validated by ANOVA. This study represents the first investigation involving the production and photocatalytic application of nanoparticles synthesized using D. kaki peel.