Abstract In the research field of micro/nano technology, piezo-driven flexure-based positioning mechanism with large workspace and high positioning precision are really desirable for the realization of high-performance micro¬/nano scale manipulation. In order to cater for this requirement, several novel large-stroke compliant positioning mechanisms are developed and presented in this thesis: Firstly, the mechanism design of a novel compliant two-degrees-of-freedom (2-DOF) nanopositioning stage is presented. This stage has two working modes, which can be chosen to drive for meeting the requirements in different levels. The new concept “dual-mode"" is quite different from the concepts of dual-stage or macro/micro dual-drive. Besides, the established models for the mechanical performance evaluation of the stage in terms of kinetostatics, dynamics, and workspace are validated by the finite-element analysis (FEA). After a series of dimension optimizations carried out through particle swarm optimization (PSO) algorithm, a novel active disturbance rejection controller (ADRC) is employed for automatically estimating and suppressing plant uncertainties arising from the hysteresis nonlinearity, creep effect, sensor noises and unknown disturbances. The simulation and prototype test results indicate that the first natural frequency of the proposed stage is approximated to be 831 Hz, the amplification ratio in two axes is about 4.2, the workspace is 119.7x121.4 μm², while the cross-coupling between the two axes is kept within 2%. Next, a novel piezo-actuated hydraulic displacement amplifier (PHDA) based on Pascal's law and area differential principle is first proposed. After a series of optimal designs, the proposed PHDA mechanism is fabricated and tested to make a characterization. In this study, a piezoelectric (PZT) actuator P-840.20 with open-loop travel of 30 μm is employed, the experimentally results indicate that the displacement amplification ratio can reach up to 34.6, thus the maximum output displacement can achieve up to around 1.02 mm. Both theoretical derivation and prototype test results well testify the satisfactory performance of the proposed mechanism. This new amplifier can be extended to practical micro/nano manipulation applications with the requirement of millimeter scale motion range. Moreover, the development of a set of flexure-based nanomanipulators with modified differential lever displacement amplifier (MDLDA) is conducted. The mechanism kinetostatics modeling is conducted by using the Pseudo-Rigid Body (PRB) method, also, the lever deformation modeling is carried out, as well as the dimension optimizations and the mechanism performance validations which are conducted by using the PSO algorithm and the finite-element-analysis (FEA) method, respectively. With the consideration of hysteresis effect inherent in PZT actuators, the hysteresis modeling is conducted by using the Preisach method. A novel feedforward nonlinear Proportion-Integration-Differentiation (FNPID) control strategy combining the nonlinear PlD controller with the inverted Preisach hysteresis compensator is proposed in this paper. Finally, the closed-loop motion tracking experiments have been carried out. All the results uniformly indicate that the displacement amplification ratio of the left and the right nanomanipulators can reach up to 30.6 and 17.6 respectively, thus, the output displacement of the fabricated micromanipulator can achieve up to 3.1273 mm and 0.528 mm respectively, and the maximum rotation angle can achieve 26.5°. Finally, a novel robotic biomanipulation system based on the developed nanomanipulators is proposed. After kinematic calibrations, the practical Zebrafish Embryo micromanipulation experiments are successfully implemented by using the developed sub-pixel scale hybrid visual control (SSHVC) strategy. All the results uniformly confirm that the developed system can be extended as an innovative method to perform biomanipulations in inaccessible or enclosed spaces.