The subject of this perspective is the application of two-dimensional (2D) layered materials in surface-enhanced Raman spectroscopy (SERS). 2D materials are regarded as promising SERS substrates because of their inexpensive and non-toxic characteristics. However, compared with the traditional precious metal substrates, its enhancement factor and detection limit are lower. In this perspective, seven advanced strategies that can improve the SERS properties of 2D materials are highlighted, including layer-dependent strategy, defect engineering, regulation of excitation laser, electric field modulation, phase engineering, arrangement mode and heterostructure design. In addition, the enhancement mechanism, synthesis strategy and application status of typical examples of molybdenum disulfide (MoS2) and MXenes as SERS substrates are discussed in detail. Finally, the prospect of future progress in SERS and possible challenges of 2D layered materials have been put forward.