The aim of this study was to improve the skin accumulation of hydroxycitric acid by using ethosomes with nanosize. We fabricated nanosized ethosome for the topical delivery of hydrophilic hydroxycitric acid and evaluated their physical properties and furthermore cytotoxicity. As results, in cell-based experiments, the use of ethosomes encapsulating hydroxycitric acid extract reduced the lipid droplet deposition in differentiated adipocytes, which was visualized by Oil Red O staining assay and also quantitatively measured by a triglyceride assay. The observed reduction in lipid droplet deposition occurred in a hydroxycitric acid extract concentration-dependent manner. In addition, the high accumulation of hydroxycitric acid in murine skin (66.28%) was observed following treatment with hydroxycitric acid extract-loaded ethosomes compared with treatment with hydroxycitric acid alone (1.19%) without ethosome as a nanocarrier. Based on these results, our findings showed that nanosized ethosomes improved the topical delivery of hydroxycitric acid and thus reduced lipid droplet deposition in adipocytes.