Allergic diseases are driven by key mediators such as thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and GATA-3, which regulate Th2 responses and eosinophilic inflammation. This study explored natural compounds that modulate these pathways. Baicalein from Scutellaria baicalensis inhibited TSLP signaling, reducing eosinophil infiltration in animal models. Lignans from Machilus thunbergii suppressed STAT5 phosphorylation and disrupted TSLP/TSLPR interactions in mast cells. Targeting IL-33, extracts from Astragalus membranaceus roots and Canavalia gladiata pods exhibited potent IL-33 inhibition, with triterpenoid saponins and flavonoid glycosides showing dose-dependent suppression of IL-33 signaling. Additionally, stilbene-containing compounds were identified as inhibitors of GATA-3–mediated transcription by binding to its zinc finger domain. These findings highlight the potential of bioactive natural compounds for developing novel antiallergic therapies.