Microvalves can play an essential role in transport and control of fluids for biomedical applications. These valves may face reliability issues as they can fail due to deterioration of the moving parts exposed to prolonged and repeated movements or handling fluids that contain particles of several microns in diameter. An alternative to valves with moving parts are microdiodes such as micro vortex diode, which offers high resistance to flow in one direction and much smaller resistance in the opposite direction. The present study is focused on developing a two-step computationally-based approach for design and optimization of micro vortex diodes. A numerical design optimization based on the Design of Experiment and Response Surface Method is employed to improve the efficiency of a micro vortex diode using geometrical parameters. The results of the optimization study suggest an optimal design with about 69% improvement in efficiency compared to the reference design.