In this paper, we propose a new in-plane XYθz nano-positioning stage that utilizes piezoelectric actuators and flexure mechanisms. The proposed stage has an aperture and is compact, which facilitates its application in measurement equipment, especially those used for biological specimens. The stage has four piezoelectric actuators and four bridge-type flexure mechanisms, which are used to amplify the small motions produced by the piezoelectric actuators. This paper describes the modeling and design optimization of the stage, which has X- and Y-direction motion ranges of 300 μm and a θz-direction motion range of ±3.9 mrad. The stage measures 150 × 150 × 23 mm, and its aperture is 50 × 50 mm.