Transdermal drug delivery is widely investigated as an alternative drug administration route to oral delivery and hypodermic injections. Owing to the availability of human skin samples, in vitro tests are used to predict the in vivo delivery of transdermal drugs. The most widely used validation method is skin permeation using diffusion cells. Traditional diffusion cells, however, are capacious and often require large amounts of skin sample and drugs, which is undesirable, given the scarcity of new drug entities and the limitation of skin sample supply. In this study, we fabricated miniaturized multichannel devices (MCDs) by 3D printing, to minimize the use of skin and drug samples. The MCDs were compared with conventional static diffusion cells and achieved comparable drug permeation profiles. The finite element method-based simulation revealed the efficient carry-off of permeated ingredients by the multichannel devices, and a critical role of distance between the buffer stream and skin sample in determining the flow velocity inside the chamber. The results support these devices as qualified alternatives to Franz cells for in vitro permeation studies using biomembranes, with reduced use of skin and drug samples.