Computer numerical control machine tool is a typical complex product related with multidisciplinary fields, complex structure, and high-performance requirements. It is difficult to identify the overall optimal solution of the machine tool structure for their multiple objectives. A new integrated multidisciplinary design optimization method is then proposed by using a Latin hypercube sampling, a Kriging approximate model, and a multi-objective genetic algorithm. Design space and parametric model are built by choosing appropriate design variables and their value ranges. Samples in design space are generated by optimal Latin hypercube method, and design variable contributions for design performance are discussed for aiding the designer's judgments. The Kriging model is built by using polynomial approximation according to the response outputs of these samples. The multidisciplinary design model is established based on three optimization objectives, that is, setting mass, optimum deformation, and first-order natural frequency, and two constraints, that is, second-order natural frequency and third-order natural frequency. The optimal solution is identified by using a multi-objective genetic algorithm. The proposed method is applied in a multidisciplinary optimization case study for a typical computer numerical control machine tool. In the optimal solution, the mass decreases by 3.35% and the first-order natural frequency increases by 4.34% in contrast to the original solution.