2D ferroelectric materials have attracted much interest due to their potential for developing flexible self‐powered nanogenerators. Niobium oxide diiodide (NbOI2) has in‐plane anisotropy of electrical properties and large lateral piezoelectric coefficient, which makes it possess high‐performance and unique behavior in flexible sensing. In this work, multidirectional piezoelectric nanogenerator (PENG) devices using NbOI2 flake are fabricated and excellent energy harvesting and sensing capabilities are found. Specifically, the NbOI2‐based PENG can exhibit a long‐time stable voltage output of 215 mV at a large strain of 1.1%. More importantly, the periodic output signal pattern of the twelve‐electrode NbOI2‐based PENG in six directions is investigated, and this anisotropy provides the possibility of achieving simultaneous signal harvesting in multiple directions. This work broadens the scope of applications of 2D materials in nano‐energy and provides new ideas and insights for further exploration of nano‐energy and smart wearable nano‐electronic devices.