This paper presents the design methodology and dynamic modelling of a piezo-driven flexure-based Scott–Russell mechanism for nano-manipulations. Based on finite element analysis, the Scott–Russell mechanism is monolithically constructed to provide high positioning accuracy and long-term repeatability. With consideration for the effect of the driving circuit, the dynamic model of the flexure-based Scott–Russell mechanism is established. The influence of the time constant RC on the dynamic response is investigated. The transient responses of the flexure-based Scott–Russell mechanism to three typical signals are derived based on the Laplace transform method. It is noted that the cycloidal command signal can generate vibration-free motion, and thus improve the dynamic performance of the flexure-based mechanism. Experimental tests have been carried out to verify the developed Scott–Russell mechanism and the established models.