Non-invasive deep brain stimulation is a novel field of research that aims to affect deep brain regions’ activity through non-invasive stimulation. Recent computational and clinical findings have fostered the interest on transcranial direct current stimulation as non-invasive deep brain stimulation techniques, and several optimization strategies have been tested. Multi-electrode transcranial direct current stimulation has shown the potential to selectively affect deep brain structures. Here, we assess whether arbitrarily chosen monopolar multi-electrode transcranial direct current stimulation montages might selectively affect deep brain structures through computational predictions and neurophysiological assessment. Electric field distribution in deep brain structures (i.e., thalamus and midbrain) were estimated through computational models simulating transcranial direct current stimulation with two monopolar and two monopolar multi-electrode montages. Monopolar multi-electrode transcranial direct current stimulation was then applied to healthy subject, and effects on pontine and medullary circuitries was evaluated studying changes in blink reflex and masseter inhibitory reflex. Computational results suggest that transcranial direct current stimulation with monopolar multi-electrode montages might induce electric field intensities in deep brain structure comparable to those in grey matter, while neurophysiological results disclosed that blink reflex and masseter inhibitory reflex were selectively modulated by transcranial direct current stimulation only when cathode was placed over the right deltoid. Therefore, multi-electrode transcranial direct current stimulation (anodes over motor cortices, cathode over right deltoid) could induce significant electric fields in the thalamus and midbrain, and selectively affect brainstem neural circuits. Such strategy should be further explored in the context of non-invasive deep brain stimulation.