Excessive exposure to sun can harm the skin, causing sunburn, photo-aging, and even skin cancer. Different benzylidene derivatives (A02-A18 and A19-A34) of 18β-Glycyrrhetinic acid (A01) were designed and synthesized in an effort to discover photo-protective compounds against UV-B -induced skin aging. The synthesized derivatives were subjected to cellular viability test using MTT assay in primary Human Dermal Fibroblasts (HDFs). The results indicate A01, A05, A15, A22, A23, A25, A26, A28, A29, A32, A33, and A34 significantly enhanced cell viability of HDFs. Compound A33 at 10 and 25 μM showed a significant photo-protective effect against UV-B (10 mJ/cm