The present study evaluates the thermodynamic, kinetic, and isotherm parameters of the adsorption of two cationic dyes as well as the optimization of their removal process using fish bone as the adsorbent. The determination of isoelectric pH (pH ZPC ) of the adsorbent demonstrated that the surface of the fish bone was negatively charged at high pH values, which could adsorb cationic dye molecules. The Langmuir, Freundlich, and Tempkin adsorption isotherms were investigated and the results showed that the removal of both dyes followed Tempkin isotherm. Adsorption kinetic studies indicated that the dye removal conformed to pseudo-second-order kinetic model; and calculation of the thermodynamic parameters revealed that the adsorption process was spontaneous (ΔG < 0) and endothermic (ΔH > 0). Also, the response surface methodology was employed for the design of experiments in binary systems using the mixture of both dyes; and the effect of operating parameters (pH, initial dye concentration, adsorbent dosage, and time) was investigated and the removal process was optimized. Eventually, the results indicated that the fish bone can be used as a proper adsorbent for the removal of cationic dyes from multi-component colored wastewaters.