A regional integrated energy system (RIES) is usually connected with an active distribution network (ADN) through an electrical interface, and participates in the ADN demand response dispatch. To improve the interaction efficiency of RIES and ADN, a two-level game optimal scheduling strategy for ADN with multiple RIES is proposed. In RIES, a heterogeneous energy optimization and coordination scheduling strategy is established to meet the demands of electricity-gas-heat load of the RIES, and to respond to ADN electricity demand scheduling with the goal of maximizing RIES benefit. A two-layer game scheduling model of ADN and RIES-coalition is established. The upper layer is the non-cooperative game between ADN and RIES-coalition, and the ADN guides RIES-coalition to formulate power purchase and sale strategies responding to the ADN demand scheduling through a time-of-use purchase and sale price policy. The lower layer is RIES-coalition members’ cooperative game to achieve the optimal distribution of coalition trading power among members, and cooperation benefits are shared among coalition members based on the Shapley value. The particle swarm optimization algorithm is used to solve the Nash equilibrium point of the game model, and the optimal electricity price strategy and the optimal electricity purchase and sale strategy of each RIES are obtained. The results of a numerical example show that the proposed strategy can improve the peak shifting and valley filling capacity of ADN, ensure the economy of RIES and the reliable operation of the ADN. This work is supported by the National Natural Science Foundation of China (No. 51607105) and the Natural Science Foundation of Hubei Province (No. 2016CFA097).