Aiming at the network structure design problems of facility location, path planning, and flow distribution in an e-commerce closed-loop supply chain network under an uncertain environment, the uncertainties of both the forward and reverse logistics demands and the impact of facility disruptions are analyzed. A robust optimization model is established using the robust peer-to-peer optimization method. An algorithm is designed that combines the minimum spanning tree algorithm with a two-layer adaptive genetic algorithm (Prim-DMGA) to solve the model. The results show that the Prim-DMGA not only requires less computation time, but also generates solutions of higher quality. In addition, the application of the robust optimization model reduces the adverse effects of uncertain factors on the e-commerce closed-loop supply chain network, thereby improving its robustness.