The state of melatonin confined either in dry lecithin or bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) reversed micelles has been investigated by H-1-NMR and FT-IR spectroscopies as a function of the melatonin to surfactant molar ratio (R). The analysis of experimental results leads to hypothesize that, independently of R and the surfactant nature and as a consequence of anisotropic melatonin/surfactant interactions, melatonin is totally solubilized in reversed micelles and mainly located by opportune orientation in the nanodomain constituted by the surfactant head groups. The absence of significant spectral changes related to the protons linked to the first carbon atoms of surfactant alkyl chain, indicates a scarce insertion of melatonin into the so-called micellar palisade layer. The possible biological implications of the peculiar solubilization state of melatonin in reversed micelles are discussed.