ABSTRACT The interest toward greener and more sustainable chemical processes is constantly growing, especially in chemical industries, where there is an urgent need to reduce the waste on one hand, and to replace not environmentally friendly organic solvents, on the other. One of the current challenges in industrial processes is the depletion of the psychoactive cannabinoid tetrahydrocannabinol (THC) from hemp extracts. Indeed, current legislations impose that THC in hemp products must meet defined concentration limits or, in some cases, it must be completely removed. In the present study, the continuous depletion of THC has been performed through simulated moving bed chromatography operated with a fully green mobile phase, made of water and ethanol. This process permits to overcome the limits and drawbacks of available purification methods, based on toxic solvents and traditional single column chromatography.