A simple, sensitive, and reliable method for the voltammetric determination of roxithromycin (RM) at the surface of the fabricated poly(3,4-ethylenedioxythiophene) (PEDOT) modified Au electrode has been successfully developed. The electrochemical behavior of RM at the surface of the modified electrode was investigated by cyclic voltammetry and differential pulse voltammetry. The influence of experimental parameters including PEDOT modified various solid electrodes, supporting electrolytes, nano-modified materials, buffer solutions, pH values and scan rates on the response of RM were studied. Under optimal conditions, the as-prepared modified electrode can be employed to the quantification of RM with a linear range covering from 0.08 to 20μM, a high sensitivity of 0.9921μAμM−1, and a low detection limit of 0.0267μM. Furthermore, the proposed modified electrode displayed high stability, good reproducibility and high sensitivity. The voltammetric determination of RM content in its capsule samples by using the as-prepared modified electrode also showed a satisfactory result with the good recovery in the range from 98.9% to 102.0%. The good result on the voltammetric determination of RM also indicated that the as-fabricated PEDOT modified Au electrode will be a good candidate for the electrochemical determination and analysis of other macrolide antibiotics.