Large airport terminals consume significant energy due to their extensive ventilation demands. Optimizing the operation of ventilation systems is a crucial aspect of achieving greater energy flexibility and efficiency. In this study, we proposed an optimal CO2-based demand-controlled ventilation (DCV) strategy that utilizes the large indoor space of airport terminals to shift ventilation loads, reduce operating cost, and enable demand response (DR) programs. The effect of air infiltration on ventilation demand is considered in the DCV strategy through on-site CO2 measurement. A passenger dwell model is integrated to estimate the occupancy of airport terminal based on flight schedules for dynamic ventilation control. Considering the DR signal and time-of-use tariff, an advanced evolutionary algorithm is employed to locate optimal ventilation solutions that deliver better economic performance and energy flexibility while meeting indoor air quality constraints. Using an airport terminal in Beijing, China, as a testbed, the superior performance of the proposed DCV strategy was demonstrated against a baseline strategy with a fixed outdoor air supply rate under three scenarios. Simulation results showed that the proposed DCV strategy can reduce peak energy consumption by up to 60.9% and operating costs by up to 48.6% in different scenarios. Moreover, the DCV strategy can provide a flexible trade-off between the overall energy efficiency and DR capability in the adjustable DR scenario. This study revealed great opportunities for improving the flexibility of ventilation in large-space buildings and provided an instructive case study.