Metals are pivotal elements in our daily life and industrial processes, to produce electronic devices, catalysts, smart materials and so on. However, they are mostly present as a mixture in the environment that makes their separation challenging over the past decade. Host-guest chemistry principle thoroughly has been used to design and synthesize thousands of organic receptors with high complexation ability and selectivity to certain metal ions. On the other hand, the droplet microfluidic device is well-known for its unique characteristics of fluid dynamics, such as large specific surface area and short diffusion distance making the process robust and efficient. Therefore, many reports of research employ host-guest chemistry of the droplet microfluidic system for the effective metal separation process. This chapter deals with up-to-date examples of the droplet microfluidic system application for separation of base and alkali metals, recovery of rare-earth and precious metals and removal of heavy metals either from the competitive metal system or from the real waste solution sample through solvent extraction techniques utilizing host-guest chemistry principle.