Nanoscale electromechanical and energy harvesting devices based on few-layer and monolayer two-dimensional (2D) materials with non-symmetric configuration have received enormous attention in recent years. Specifically, piezoelectric and triboelectric devices based on 2D materials for energy harvesting, physical/chemical sensing, healthcare, and optoelectronics applications have been a growing interest. In this chapter, the typical preparation methods of 2D-layered materials, such as exfoliation methods and chemical vapor phase deposition (CVD), will be discussed first. Then, various characterization techniques by atomic microscopic analysis for 2D materials will be provided briefly. Finally, future aspects of developing 2D piezoelectric and triboelectric devices and their potential applications will be introduced.