Studies have shown that stem cells and their derivatives, including conditioned media (CM), have inhibitory effects on skin pigmentation. However, evidence supporting the skin brightening effect of exosomes derived from stem cells is lacking. We studied the antipigmentation effect in vitro and skin brightening efficacy in vivo of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells (ASC-exosomes). Exosomes were isolated from the CM of ASCs using the tangential flow filtration method. ASC-exosomes reduced intracellular melanin levels in B16F10 melanoma cells regardless of the presence of the α-melanocyte-stimulating hormone (α-MSH). The skin brightening efficacy of a cosmetic formulation containing ASC-exosomes was assessed in human volunteers with hyperpigmentation in a prospective, split-face, double-blind, randomized placebo-controlled study. The ASC-exosome-containing formulation statistically decreased the melanin contents compared to the placebo control. However, the melanin-reduction activity was limited and diminished along with time. A further improvement in efficient transdermal delivery of ASC-exosomes will be helpful for more profound efficacy. In summary, these results suggest that ASC-exosomes can be used as a cosmeceutical for skin brightening.