Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model. The secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice's dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-β1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (P<0.05). UVB induction caused loss of collagen, increasing inflammation and high expression of aging mediators. SC increased the gene expression of TGF-β1 and IL-10 and decreased IL-18 gene expression. Histopathological tests showed that SG increased collagen density, lowered inflammation, and repaired cell damage in skin tissue. Immunohistochemistry test showed that SC decreased MMP-2, MMP-13, and P53 expression, in contrast, increased COL4A1. The secretome gel of hWJ-MSCs showed antiaging activities with potential for preventing and curing skin aging.