Because of their wide bandgap and ultrathin body properties, two-dimensional materials are currently being pursued for next-generation electronic and optoelectronic applications. Although there have been increasing numbers of studies on improving the performance of MoS2 field-effect transistors (FETs) using various methods, the dielectric interface, which plays a decisive role in determining the mobility, interface traps, and thermal transport of MoS2 FETs, has not been well explored and understood. In this article, we present a comprehensive experimental study on the effect of high-k dielectrics on the performance of few-layer MoS2 FETs from 300 to 4.3 K. Results show that Al2O3/HfO2 could boost the mobility and drain current. Meanwhile, MoS2 transistors with Al2O3/HfO2 demonstrate a 2× reduction in oxide trap density compared to that of the devices with the conventional SiO2 substrate. Also, we observe a negative differential resistance effect on the device with 1 μm-channel length when using conventional SiO2 as the gate dielectric due to self-heating, and this is effectively eliminated by using the Al2O3/HfO2 gate dielectric. This dielectric engineering provides a highly viable route to realizing high-performance transition metal dichalcogenide-based FETs.