Despite the recent interest in organic electrochemical transistors (OECTs) as chemical and biological sensors, little is known about the role that device architecture and materials parameters play in determining sensor performance. We use numerical modeling to establish design rules in two regimes of operation: We find that for operation as an ion-to-electron converter, the response of OECTs is maximized through the use of a gate electrode that is much larger than the channel or through the use of a nonpolarizable gate electrode. Improving the conductivity of the polymer and using a channel geometry that maximizes channel width and thickness, and minimizes channel length helps increase the response. For operation as an electrochemical sensor, the sensitivity is maximized in OECTs with gate electrodes that are smaller than their channels. The sensitivity can be improved by increasing the charge carrier mobility and the capacitance per unit area of the conducting polymer, and also its ability to be penetrated by ions from the electrolyte. A channel geometry that maximizes channel width and minimizes channel length also improves sensitivity.