© 2020 by the authors.The objective of this work is to develop a closed-loop controlled insulin pump to keep the blood glucose level of Type 1 diabetes mellitus (T1DM) patients in the desired range. In contrast to the existing artificial pancreas systems with syringe pumps, an energy-efficient, valveless piezoelectric pump is designed and simulated with different types of controllers and glucose-insulin models. COMSOL Multiphysics is used for piezoelectric-fluid-structural coupled 3D finite element simulations of the pump. Then, a reduced-order model (ROM) is simulated in MATLAB/Simulink together with optimal and proportional-integral-derivative (PID) controllers and glucose-insulin models of Ackerman, Bergman, and Sorensen. Divergence angle, nozzle/diffuser diameters, lengths, chamber height, excitation voltage, and frequency are optimized with dimensional constraints to achieve a high net flow rate and low power consumption. A prototype is manufactured and experimented with different excitation frequencies. It is shown that the proposed system successfully controls the delivered insulin for all three glucose-insulin models.