Background: The “bird's nest soup” is a kind of luxury or tonic food prepared from edible bird's nest (EBN), which is used as an extremely nutritious medicine to improve health. However, its skin anti-inflammatory and wound-healing effects are still not fully understood. Aim: In this study, the skin-protective effects of two geographical types of EBN (EBN-A and EBN-B) were investigated. Materials and Methods: The anti-aging effect was assessed in ultraviolet B (UVB)-irradiated normal human dermal fibroblasts (NHDFs), while the anti-inflammatory effect was evaluated in tumor necrosis factor alpha/interferon gamma (TNF-α/IFN-γ)-stimulated human skin keratinocytes (HaCaTs). The wound-healing activity was investigated in scratched NHDFs and hyalorunan production was examined in HaCaTs. Results: In this study, EBN showed good efficiency in scavenging free radicals. EBN notably decreased the UVB-induced matrix metalloproteinase-1 expression and promoted procollagen type I synthesis that resulted in the protective effect of EBN against UVB-induced skin damage. Overexpression of thymus- and activation-regulated chemokine and macrophage-derived chemokine induced by TNF-α/IFN-γ was significantly decreased after treatment with EBN at 1–10 μg/ml. The most effective wound healer was EBN-B at 1–10 μg/ml, based on the high expression of hyaluronan that has long been associated with the remodeling extracellular matrix in wound healing. Conclusion: These results indicate that EBNs have the potential to ameliorate UVB-induced skin photo aging and NF-α/IFN-γ-stimulated inflammation as well as wound injuries, resulting in rapid healing effects.