Molybdenum disulfide (MoS2) is a two-dimensional material that exhibits unique interfacial interactions with metals, making it potential coating material for improving material properties of metals. In this work, the effects of multilayer MoS2 coating on the mechanical properties and deformation behaviours of copper (Cu) and gold (Au) substrates are investigated by nanoindentation experiments and molecular dynamics (MD) simulations. Specifically, our experimental results indicate that the MoS2 coating greatly increases the Young's modulus and hardness of Au substrate throughout the indentation process. In the MoS2/Cu system, however, the MoS2 coating exhibits inverse effects at diffident indentation depths, which, specifically, has the weakening and enhancing effects at the early and late stages of the indentation process, respectively. MD simulations indicate that the different effects of the MoS2 coating on the mechanical properties of Au and Cu substrates are attributed to the different interfacial adhesion properties between the MoS2/Cu and MoS2/Au systems, as the binding energy of the MoS2/Au system is much larger than that of its MoS2/Cu counterpart. Moreover, it is also revealed in MD simulations that the load-bearing area of metal substrates can be significantly enlarged by the MoS2 coating, which leads to the dense dislocations distributed in metal substrates and thus the strain-hardening in MoS2/metal composites.