Gallium-based liquid metals (GaLM) are promising for a variety of applications, especially as component materials in soft devices, due to their fluidity, low toxicity and reactivity, and high electrical and thermal conductivity compared to solids. Understanding the interfacial properties and behavior of GaLM in various environments is critical for most applications. GaLM forms a nanoscale thick layer of gallium oxide when exposed to air or water. This “oxide nanoskin” can passivate metal surfaces and form stable microstructures and films despite the high surface tension of liquid metal. Oxide skin adheres easily to most smooth surfaces. Although it enables effective printing and patterning of GaLM, it can also make the metal difficult to handle. Oxides also affect the interfacial electrical resistance of metals. Their formation, thickness and composition can be controlled chemically or electrochemically, altering the physical, chemical and electrical properties of the metal interface. Without oxide, GaLM wets metal surfaces but not non-metallic substrates such as polymers. The topography of the underlying surface further influences the wetting properties of the metal. In this review, we briefly describe the interfacial properties of GaLM in air, water and other environments and discuss related applications based on interfacial engineering. The influence of surface topography on the wetting behavior of GaLM is also discussed. Finally, we suggest important research topics to better understand the GaLM interface.