Significant effects of maghemite (gamma-Fe2O3) nanoparticles on the voltammetric behavior of carbon paste electrode for bio determination of dipyridamole (DIP) were studied. The electrochemical performance of maghemite NPs modified carbon paste electrode (MMCPE) was investigated (compared to unmodified and the other manufactured modified electrodes) and the mechanism was studied by using differential pulse voltammetry (DPV) and cyclic voltammetry (CV) techniques. Herein we utilized statistical based experimental design for simple optimization of effective parameters on the response of the electrode. Results indicate that MMCPE can remarkably enhance electrocatalytic activity toward the oxidation of dipyridamole (DIP) in Britton-Robinson buffer at pH 2.0. Under optimal conditions a detection limit of 5.0 x 10(-9) mol L-1 (2.5 ng mL(-1)) was obtained by DPV. The advantageous method was then tested for the simple, rapid and sensitive electrochemical determination of DIP in pharmaceutical formulations and human plasma as real samples. (C) 2013 The Electrochemical Society. All rights reserved.