The aim of this research was to apply experimental design methodology to optimization of conditions of electrochemical oxidation of Rhodamine B (RhB) and N, N-Dimethyl-4-nitrosoaniline (RNO, indicative of the OH radical). The reactions of electrochemical oxidation of RhB degradation were mathematically described as a function of the parameters of current ($X_1$), NaCl dosage ($X_2$) and pH ($X_3$) and modeled by the use of the central composite design. The application of response surface methodology (RSM) yielded the following regression equation, which is an empirical relationship between the removal efficiency of RhB and RNO and test variables in a coded unit: RhB removal efficiency (%) = $94.21+7.02X_1+10.94X_2-16.06X_3+3.70X_1X_3+9.05X_2X_3-{3.46X_1}^2-{4.67X_2}^2-{7.09X_3}^2$; RNO removal efficiency (%) = $54.78+13.33X_1+14.93X_2- 16.90X_3$. The model predictions agreed well with the experimentally observed result. Graphical response surface and contour plots were used to locate the optimum point. The estimated ridge of maximum response and optimal conditions for the RhB degradation using canonical analysis was 100.0%(current, 0.80 A; NaCl dosage, 2.97% and pH 6.37).