Small interfering RNA (siRNAs) is a double-stranded RNA molecule which can hybridize with a specific mRNA sequence and block the translation of numerous genes to regulate endogenous genes and to defend the genome from invasive nucleic acids. The use of siRNAs has been studied as a treatment option for various skin conditions. One of the main obstacles in the dermal or transdermal delivery of this compound is low skin permeability, and application is limited by its negative charge, high polarity, susceptibility to degradation by nucleases, and difficulty in penetrating the skin barrier. Effective delivery of therapeutic biomolecules to their target is a challenging issue, which can be solved by innovations in drug delivery systems and lead to improvement of the efficiency of many new biopharmaceuticals. Designing of novel transdermal delivery systems garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries, which offers a number of advantages. Developing safe and efficient siRNAs delivery vectors is essential for effective treatment of skin diseases. In recent years, significant progress has been made in the creation of delivery systems using lipids, polymers, cell-penetrating peptides, nanoparticles and other biologically active agents. In this review we will focus on the recent advancements in transdermal siRNAs delivery vectors, such as liposomes, dendrimers, cell-penetrating peptides, and spherical nucleic acid nanoparticles.© 2023 The Authors.