The present paper describes a voltammetric sensor based on glassy carbon electrode (GCE) modified with a thin film of multi-walled carbon nanotubes (MWCNTs) coated with an electro-polymerized layer of titan yellow-doped over-oxidized polypyrrole (OPPY) for the determination of tizanidine (TIZ). A significant enhancement was observed in the anodic peak current of TIZ on the surface of OPPY/CNT/GCE, relative to the bare, CNT- and OPPY-coated GCEs. The microscopic structure and surface morphology of the composite film was thoroughly characterized by means of atomic force microscopy (AFM), scanning electron microscopy (SEM) and cyclic voltammetry (CV) techniques. The effect of various experimental parameters, such as pH of the supporting electrolyte, drop size of the casted MWCNTs suspension, number of electro-polymerization cycles and accumulation time were investigated by monitoring the LSV responses of TIZ. In the optimal conditions, the modified electrode showed two linear dynamic ranges of 0.01-1.0 mu M and 1.0-10 mu M with a detection limit of 3 nM for the voltammetric determination of TIZ. Besides high sensitivity, the fabricated sensor represented high stability and good reproducibility for TIZ analysis. These properties made the prepared sensor suitable for the accurate determination of trace amounts of TIZ in pharmaceutical and clinical preparations.