A novel, simple, sensitive, and highly selective omeprazole sensor based on the synergistic effect of polyaniline (PANI) and multiwalled carbon nanotubes (MWCNTs) has been developed. The morphology and electroanalytical performance of the fabricated sensor were characterized by scanning electron microscopy, square-wave voltammetry, and cyclic voltammetry. The influence of various parameters such as pH, effect of scan rate, and loading of PANI-MWCNTs hybrid film onto glassy carbon electrode (GCE) on electroanalytical performance of the developed sensor was investigated. The modified electrode showed an excellent electrocatalytic activity toward the reduction of omeprazole resulting in a considerable improvement of the peak current as compared to the electrochemical activity at the bare glassy carbon electrode. The incorporation of PANI with MWCNTs increased the peak current and electrochemical reactivity of omeprazole in comparison to that at the MWCNTs and PANI film. PANI-MWCNTs composites are expected to be a promising material for biosensing applications.