Dispersion strengthening is one of the most effective methods to strengthen a metallic material. The strength of an aged alloy is largely affected by the precipitate size and number density of precipitates, which are often controlled by the change in temperature, time, and composition. Here we report a new high-pressure (HP) strategy for regulating the nanoprecipitates (NPs) in a Fe50Cr16Ni27Ti4Al3 medium-entropy alloy. Using a HP of 4 GPa largely refines the size of NPs from 15 to 4nm (due to the suppressed grain-growth rate) and increases the number density of NPs by two orders of magnitude (due to the increased nucleation rate). The decreased size and increased density of NPs lower the spacing distance of high-density dislocation walls and result in the formation of microbands during deformation, causing sustainable strain-hardening in the MEA, thereby improving both strength and ductility.