The impact of nanomedicine has grown in the current decade; however, only very few clinical translational attempts have been realized. Therefore in the present study, we hypothesized that bergamot oil, a psoralen-containing oil, would produce an optimized melanogenic effect in the clinical treatment of vitiligo when loaded within an elastic nanocarrier (spanlastics) and combined with PUVB for activation of psoralens. Spanlastics were prepared and characterized for particle size, physical stability, in vitro release, thermal behavior, deformability, morphology, and in vitro photostability. The efficacy of the selected formula was tested histopathologically on rat skin and clinically translated in patients suffering from vitiligo. Results revealed that the spanlastics were of reasonable nanosize, deformable, and provided sustained release of bergamot oil. The incorporation of bergamot oil within spanlastics improved its photostability and its photodynamic activity. Spanlastics exhibited promising clinical results in terms of extent and onset of repigmentation in vitiligo patients. Therefore, it can be concluded that spanlastics can be introduced as a promising nanotreatment modality for vitiligo.