This paper presents a dynamic reliability-based optimization technique for the seismic design of base-isolated structures. Firstly, the governing equation of multi-degree-of-freedom base-isolated structures is established. Then, the superstructure is unfolded by the first mode. Considering that the damping is non-classical and the total base-isolation system is un-symmetric, the complex modal analysis is adopted to uncouple the governing equation and the analytical solutions of stochastic seismic response under the Kanai-Tajimi spectrum loading are obtained. Taking the ratio between the first-order modal displacement standard deviation of the superstructure with base- isolated system and the fixed-base structure as the optimal objective function, the dynamic reliability of the isolated system displacement as the constraint, the optimal design parameters of the isolated system are obtained through the penalty function method. A 3-story building with isolated system illustrates the proposed dynamic reliability-based optimization method. It is believed that such an optimization technique provides an effective tool for the seismic design of base-isolated structures.