This paper deals with the design of fractional order PID controllers based on nonlinear optimization for Multi-Input Single-Output (MISO) systems with time delays. Two approaches are used to obtain optimal controllers’ parameters. The first uses time-domain specifications and consists of minimizing time-domain criteria without constraints. The second uses frequency-domain specifications and imposes the open-loop phase to be flat in a specified frequency band. Simulations results and a comparative study are presented to verify the effectiveness of each approach.