The application of macrofiber composite (MFC) actuators to an active twist control of helicopter rotor blades significantly reduces the vibration and noise without the use of complex mechanisms in the rotating systems. The applicability of two main spar designs and two variants of utilization of MFC actuators for an active twist of advanced helicopter rotor blades is examined in the present study. For this reason, 3D finite-element models and the corresponding piezoelectric, static torsional, and modal analyses are developed using the ANSYS code. Due to the great dimension of the numerical problem to be solved, an optimization methodology is developed employing the design of experiments and the response surface technique. The numerical results found are validated successfully by quasi-static tests on a demonstration blade, which confirm the high accuracy of the 3D finite-element models developed and the corresponding analyses performed.