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<i>Sambucus nigra</i> L. (<i>S. nigra</i>) is a shrub widespread in Europe and western Asia, traditionally used in medicine, that has become popular in recent years as a potential source of a wide range of interesting bioactive compounds. The aim of the present work was to develop a topical <i>S. nigra</i> extract formulation based on ethosomes and thus to support its health claims with scientific evidence. <i>S. nigra</i> extract was prepared by an ultrasound-assisted method and then included in ethosomes. The ethosomes were analyzed in terms of their size, stability over time, morphology, entrapment capacity (EC), extract release profile, stability over time and several biological activities. The prepared ethosomes were indicated to be well defined, presenting sizes around 600 nm. The extract entrapment capacity in ethosomes was 73.9 ± 24.8%, with an interesting slow extract release profile over 24 h. The extract-loaded ethosomes presented collagenase inhibition activity and a very good skin compatibility after human application. This study demonstrates the potential use of <i>S. nigra</i> extract incorporated in ethosomes as a potential cosmeceutical ingredient and on further studies should be performed to better understand the impact of <i>S. nigra</i> compounds on skin care over the time.