A structural optimization method is proposed for designing energy supply systems in consideration of their multi-period operation. The structural optimization problem is formulated as a large-scale mixed-integer linear programming (MILP) problem with binary variables for selection and on/off status of equipment, and continuous variables for capacities and energy flow rates of equipment. A decomposition method with a strategy for partitioning variables finely is applied to solve the large-scale MILP problem. Through a numerical case study, the influence of demand characteristics on structural design of energy supply systems is clarified by the proposed method.