Background: A reduced lipid content in the stratum corneum is a major cause of skin barrier function deterioration in various diseases. Accordingly, the promotion of lipid production is a potential strategy to improve skin barrier function. Recent studies support the beneficial effects of adiponectin on lipid metabolism and senescence in keratinocytes. Objectives: We screened plant extracts that enhance the lipid synthesis of keratinocytes via sirt1-nuclear hormone receptor signaling in the adiponectin pathway. Methods: The levels of major lipid synthesis enzymes and transcription factors as well as sphingolipids, involved in adiponectin-associated keratinocyte lipid production, were evaluated in plant extracts or the adiponectin-treated human epidermal equivalent Results: Among 300 plant extracts of the phytochemical library, 20 candidates were selected through cell viability analysis and literature review. We selected fruit extracts of Lycium barbarum L., Prunus tomentosa and Melia toosendan among 20 extracts as candidates to enhance lipid synthesis of keratinocytes through sirt1-nuclear hormone receptor signaling in the adiponectin pathway. In particular, among the extracts with a detectable effect, Melia toosendan fructus showed the highest expression of lipid synthase. Conclusion: The Melia toosendan fructus extract is an appropriate material for improving skin barrier function.