Glycerol/gel is the best carrier for applying CBD to skin: Among tested vehicle solutions, the propylene glycol/water mixture (80/20, v/v) achieved the best performance both in terms of permeation rate and skin retention. The transformation of the solution into hydrophilic gel did not affect the performance in terms of permeation rate but led to a significant reduction of the amount of CBD retained in the SCE. However, the hydrophilic gel proved to be the most effective vehicle among the proposed formulations. Paraffin oil and lipophilic ointment also proved to be suitable vehicles for the administration of CBD, guaranteeing a significant permeation performance. Despite lower dosing and unfavorable thermodynamic conditions, the (trans)dermal patch provided a comparable performance in terms of skin retention.