Edible bird's nest (EBN) is a nutritious food with many beneficial effects, including protecting cells against oxidation and infection due to wounds, bacteria or viruses. EBN has shown antiaging, anti-inflammatory and wound-healing properties in skin cells. Here, we investigated whether EBN has protective effects against photoaging, inflammation and immune-senescence in hairless mice treated with UVB irradiation. The skin thickness was lower in mice on an EBN diet than in mice treated with UVB alone. The level of hydration was significantly increased, while the index of transepidermal water loss decreased, in groups on the EBN diet. EBN also reduced erythema index in UVB-irradiated mice. At the molecular level, skin elasticity and antiaging are associated with high expression of elastin, collagen and filaggrin and low expression of the membrane metalloproteinases, MMP-1 and MMP-2. Inflammatory markers such as interleukins, IL-1β and IL-6, and TNF-α decreased significantly in the EBN groups. Caspase-3, an important factor in the apoptotic pathway and in congenital and adaptive immune responses, decreased in the EBN groups. Moreover, EBN diminished the overexpression of immunoglobulin E and elevated mast cell counts in UVB-irradiated mice. Overall, these findings suggest that EBN protects skin against aging and alleviates inflammation in UVB-irradiated hairless mice.