A new protocol developed by this research for higher removal, efficiency of oil and grease and chemical oxygen demand (COD) tannery soak wastewater. After the treatment, the recycled water used for various purposes such as floor cleaning, planting, irrigation purpose. The present work investigated the feasibility of photo oxidation process for removal of oil and COD in Indian tannery soak wastewater via mathematical modelling and statistical approach. The influence of process variables such as nano-catalyst dose and reaction time was analysed on removal of oil /grease and COD. The obtained results are discussed using response surface methodology (RSM) design in detail. Zinc oxide nanoparticles prepared from Eclipta Prostrata plant leaves and characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) with Energy Dispersive X-Ray Analysis (EDX) and Transmission Electron Microscopy (TEM).