Due to the fact that organic matter in sago wastewater is not effectively removed by current traditional methods, this study was designed to systematically investigate the performance of photo-Fenton treatment. Despite being ratified for its high efficiency in improving wastewater quality, there remains a paucity of evidence on its performance on sago wastewater. Thus, the objective of this study was to optimize the conditions of the photo-Fenton process by employing the response surface methodology (RSM) using the chemical oxygen demand (COD) removal as the target parameter. Fenton’s reagent (Fe2+ and H2O2 concentration) and pH were used as the independent variables to be optimized. Under optimum conditions, 90.0% of COD removal efficiency was obtained when the wastewater sample was treated at pH 2.66 in the presence of 4.01 g/L of H2O2and 5.07 g/L Fe2+ion. Despite the high COD removal, the total organic carbon (TOC) removal under the same optimized condition was lower, only 48.0% indicating incomplete mineralization of stable intermediates present in the solution. Toxicity evaluation revealed that the mortality of Artemia salina was less than 50%, which means that the treated sago wastewater can be considered as non-toxic. The regression value (R2> 0.99) of the models indicates a high degree of correlation between the parameters evaluated. The results obtained indicate the feasibility of photo-Fenton treatment to the sago wastewater as an appealing alternative approach.