In this study, a mathematical model aiming at minimizing the total distribution distance is established for the vehicle routing problem of simultaneous delivery and pickup with time window constraints. According to the characteristics of the model, a discrete grey wolf optimization (DGWO) algorithm is proposed to solve the problem on the basis of preserving the search mechanism of the grey wolf optimization (GWO) algorithm. Multiple strategies are adopted to construct the initial solution of the population, and the unfeasible solution is allowed to expand the search area of the population; the neighborhood search strategy with scoring strategy is introduced to adjust the probability of each operator so that the algorithm can select the operator with better optimization effect; the deletion-insertion mechanism is used to explore the high-quality solution region and accelerate the convergence of the population. The standard data set is tested in the simulation experiment, and the experimental results are compared with the p-SA algorithm, DCS algorithm, VNS-BSTS algorithm, and SA-ALNS algorithm. The experiment shows that the DGWO algorithm can effectively solve the vehicle routing problem of simultaneous delivery and pickup with time window constraints.