This study was performed on an aqueous extract of baobab seedcake enriched in small ribonucleic acids (RNAs) for cosmetic use. The seedcake is a by-product, obtained from Baobab seeds belonging to the Adansonia digitata species. A particular patented extraction process, named plant small RNA (PSR) technology, has been developed to retain some specific nutrient compounds, including small RNAs. Small RNAs, such as microRNAs (miRNAs), play an essential role in gene regulation. The biological potential of this new patented PSR extract was studied in skin fibroblasts and in ex vivo skin. To demonstrate the effect relative to the presence of small RNAs, the same extract in which small RNAs were removed was also tested. After observing the efficacy of PSR extract on collagen expression in ex vivo skin, different markers of senescence were investigated on fibroblasts aged by replicative senescence. The study of the expression of Drosha, an enzyme responsible for miRNA maturation, the expression of miRNA-19b, a biomarker of cellular aging, and the activity of senescence-associated β-galactosidase showed more efficient activity of PSR extract, compared with small RNAs-free extract. Taken together, these studies demonstrate the potential of PSR extract for use in cosmetic end use applications.