This paper deals with the adaptive neural network control of a nonlinear rigid-flexible manipulator subject to external disturbances and multiple constraints. The system dynamic is modeled by ordinary and partial differential equation (ODE and PDE) based on Hamilton’s Principle. An adaptive neural network sliding mode control strategy is designed to estimate the unknown disturbances and uncertain parameter. The sliding surface consisting of angular error, angular velocity error, and end-point vibration information is proposed based on the energy analysis of the flexible beam. The tangent barrier Lyapunov function is used to ensure the angle errors and end-point deflection within the restrictions. It is shown that the joint motion and vibration of the flexible beam can be adjusted only with an independent joint control input, and no boundary force input is required for vibration suppression. The stability is obtained by semi-group theory and LaSalle’s Invariance Principle. Simulation results demonstrate the effectiveness of the control strategy.