The production of menthol-loaded poly-e-caprolactone nanoparticles (NPs) for dermal application was investigated. The nanoparticles were produced in three different mixers: a confined impinging jet mixer (CIJM), a two-inlet vortex mixer (VM), and a four-inlet vortex mixer (MIVM), testing their performances in the same operating conditions. The effects of various process parameters such as polymer and menthol concentration, flow rate, solvent type (acetone, acetonitrile, or THF), and quench ratio, on mean nanoparticle size, menthol loading, and encapsulation efficiency were compared and discussed. The amount of menthol encapsulated inside the nanoparticles was quantified by GC analysis and the structure and shape of the NPs were analyzed by TEM. Nanoparticles of sizes between 200 nm to 800 nm were obtained using the CIJM, the VM, and the MIVM with different feeding sequences. It was observed that mixer geometry had a strong effect on particle size (at the same operating conditions the size decreased from MIVM with two inlets to VM and to CIJM) and the smallest particles were obtained using the MIVM using one solvent and three antisolvent streams. By using acetonitrile, the mean nanoparticle size was larger. Incorporation efficiency and menthol loading values up to 80 % and 60 % respectively were obtained depending on the inlet menthol and polymer concentrations.