Removal efficiencies of color and chemical oxygen demand (COD) after TiO2-mediated photocatalytic degradation process of synthetic wastewaters prepared using Methylene Blue as a fairly toxic textile dye were quantified in the present study. For this purpose, effects of lamp type, initial dye concentration (mg/L), catalyst dose (g/L), reaction time (min), aeration (mL/min), temperature (oC), and initial pH were considered using design of experiments (DOEs). Plackett-Burman Design and Fractional Factorial Design were set to screen for the most influential explanatory variables. Box-Behnken Design and Central Composite Design as optimization designs were used in the optimization of the significant predictors detected. 3-D response surface plots and ANOVA results demonstrated that ultraviolet-C yielded the highest removal efficiencies of color and COD, with a significant interaction effect of aeration by catalyst dose on the removal efficiencies.