A machine-tool structure optimization is an important technique that improves the machining efficiency and saves materials and the energy resource. In this work, dynamic design optimization method for Machine-Motorized-Spindle (MMS) subjected to a number of rotating unbalanced forces effects is presented. Linear forced-Rotordynamic analysis with design explorer method has been used to simulate the output response. The Design Variables (DVs) and their limits were carefully chosen and applied to develop the Design-of-Experiment (DOE). The Box-Behnken Design (BBD) method, because of its good organization in providing much information in a minor number of required statistical experiments was used to generate the DOE. The influences of DVs on the dynamic of MMS and their levels optimization were evaluated by utilizing the Response-Surface (RS) method. The results showed that the spindle shaft inner diameter of the motor-rotor seat and its rotating unbalanced mass, and modulus of elasticity have the highest contribution in effect on the dynamic of MMHS. As well, it is found that the proposed optimization method not only improves the structural weight of MMS, but also the potential saving can be achieved in term material and energy resource.