Since most spacecraft multiple-impulse trajectory optimization problems are complex multimodal problems with boundary constraint, finding the global optimal solution based on the traditional differential evolution (DE) algorithms becomes so difficult due to the deception of many local optima and the probable existence of a bias towards suboptimal solution. In order to overcome this issue and enhance the global searching ability, an improved DE algorithm with combined mutation strategies and boundary-handling schemes is proposed. In the first stage, multiple mutation strategies are utilized, and each strategy creates a mutant vector. In the second stage, multiple boundary-handling schemes are used to simultaneously address the same infeasible trial vector. Two typical spacecraft multiple-impulse trajectory optimization problems are studied and optimized using the proposed DE method. The experimental results demonstrate that the proposed DE method efficiently overcomes the problem created by the convergence to a local optimum and obtains the global optimum with a higher reliability and convergence rate compared with some other popular evolutionary methods.