This paper reports the nonlinear dynamic modeling and the optimal trajectory planning for a flexure-based macro-micro manipulator, which is dedicated to the large-scale and high-speed tasks. In particular, a macro- micro manipulator composed of a servo motor, a rigid arm and a compliant microgripper is focused. Moreover, both flexure hinges and flexible beams are considered. By combining the pseudorigid-body-model method, the assumed mode method and the Lagrange equation, the overall dynamic model is derived. Then, the rigid-flexible-coupling characteristics are analyzed by numerical simulations. After that, the microscopic scale vibration excited by the large-scale motion is reduced through the trajectory planning approach. Especially, a fitness function regards the comprehensive excitation torque of the compliant microgripper is proposed. The reference curve and the interpolation curve using the quintic polynomial trajectories are adopted. Afterwards, an improved genetic algorithm is used to identify the optimal trajectory by minimizing the fitness function. Finally, the numerical simulations and experiments validate the feasibility and the effectiveness of the established dynamic model and the trajectory planning approach. The amplitude of the residual vibration reduces approximately 54.9%, and the settling time decreases 57.1%. Therefore, the operation efficiency and manipulation stability are significantly improved.