A forced response induced by inlet distortion and blade row interactions can lead to high-cycle fatigue failure, especially when the unsteady excitation frequency is close to the natural vibration frequency of a blade. This paper presents the study of forced response sensitivity analysis and minimization using a full-viscosity unsteady discrete adjoint method. The goal is to improve the aeroelastic performances of turbomachinery blades and simultaneously constrain/improve aerodynamic performances. The decoupled modal reduction method is used to compute the forced response, which is considered the objective function in adjoint-based design optimization. To analyze aeroforcing and aerodamping flow and adjoint fields efficiently, the harmonic balance method and its adjoint counterpart developed by an automatic differentiation tool are applied. Two cases—the NASA Rotor 67 with inlet distortion and a three-row configuration with multiple fundamental frequencies in the second row—are used to demonstrate the effectiveness of the aerodynamic and aeroelastic coupled design optimization system developed in this work. For the latter case, the Fourier-transform-based method that first decomposes and then matches the time and space modes at two sides of an interface is used for interface coupling. The almost-periodic Fourier transform method is used to determine the time instances for cases with multiple fundamental frequencies.