Background: Bone marrow-derived mesenchymal stem cell (BM-MSC) is a representative and classic stem cell applied widely for clinical aspects, especially in the fields of myocardial and hepatic regeneration. Objectives: This clinical trial aims to evaluate the anti-wrinkle effect and safety of BM-MSC conditioned media. Methods: The tried cosmetic product contains the active ingredients of BM-MSC conditioned media, while the control product has no active ingredients. 29 subjects were finally selected and randomly applied each product to the left or right side of the face twice a day for 8 weeks. Results: The participants were women aged between 36 and 55 with the average age of 43.7. In visual evaluation, 13 subjects showed better results on the treated area, whereas 8 subjects on the control area. Based on clinical pictures, there was a significant wrinkle reduction rate on the treated area. The wrinkle reduction rate on the treated area was 12.0% on average, compared with -1.25% on the control area in 4 weeks (p<0.001), and 23.31% on the treated area compared with 3.84% on the control area in 8 weeks (p<0.001). In replica analysis, significant decreases in wrinkles length (8 weeks) and wrinkles depth (4 and 8 weeks) were identified in treated area. Only a few mild side-effects were associated with BM-MSC conditioned media. Conclusion: In conclusion, an anti-wrinkle cosmetic product with BM-MSC conditioned media could significantly improve wrinkles with less and very slight side-effects.