Two-dimensional (2D) transition-metal disulfides (TMS2) are promising functional components to construct a large variety of sensing devices. The rational engineering on their interlayer structures has recently demonstrated the capability of modulating electronic configurations and optical properties toward benchmarking performance. In this review, representative efforts and progress made on interlayer-engineered TMS2 sensors are comprehensively reviewed, focusing on the intrinsic relationship between interlayer chemistry and sensing behaviors. Briefly, effective strategies mainly including intercalation and exfoliation are expatiated for effective interlayer engineering, and thereby for feasible modulation on electronic and optical properties. And then, the characteristic electrochemical and optical sensing performances are summarized to highlight the key promotion via interlayer-engineering. Finally, a perspective on the future development of 2D TMS2 is offered. The overall aim of this review is to shed some light on the exploration of emerging materials in sensing fields.