Molybdenum disulfide (MoS₂), a representative two-dimensional (2D) transition metal dichalcogenide, has attracted growing attention due to its intrinsic piezoelectric properties in monolayer and few-layer configurations. This chapter provides a comprehensive overview of the fundamental mechanisms, synthesis strategies, and structural engineering techniques used to enhance the piezoelectric performance of MoS₂. Key topics include the origin of piezoelectricity in non-centrosymmetric MoS₂, the role of doping, strain modulation, and interface engineering, as well as the development of nanostructures such as nanoribbons, and nanosheets. Fabrication methods ranging from mechanical exfoliation to chemical vapor deposition and atomic layer deposition are discussed in the context of material quality and device applicability. The practical implications of MoS₂ piezoelectric nanomaterials are explored across a wide range of applications, including energy harvesting, flexible electronics, biomedical sensing, and piezocatalysis. Finally, current challenges and future directions are highlighted to guide further research in this rapidly evolving field. This chapter aims to provide a timely and critical understanding of MoS₂-based piezoelectric systems, facilitating their advancement toward high-performance, scalable, and multifunctional applications in next-generation technologies.