Although the polyphenols have been studied to alleviate inflammation, there are still challenges to delivering the polyphenols with stabilized formulation due to the low water solubility and susceptibility to oxidation. We herein developed the transdermal delivery system of polyphenol mixture (PM), including quercetin (Q), phloretin (P), and ellagic acid (E), using double emulsion for applying to atopic dermatitis (AD). Through the in vitro anti‐degranulation assay, we obtained the optimal molar ratio of each polyphenol (Q:P:E = 5:1:1), and the PM showed at most a 43.6% reduction of degranulation of immune cells, which is the primary factor of AD. Moreover, the water‐in‐oil‐in‐water double emulsion (W/O/W) enhanced the PM's stability and had a higher anti‐degranulation effect than the oil‐in‐water emulsion (O/W). In the in vivo 1‐chloro‐2,4‐dinitrobenzene (DNCB)‐induced mice AD model, PM reduced more AD symptoms than every single polyphenol. The PM‐encapsulated W/O/W (PM_W/O/W) showed the most effectiveness in AD by decreasing dermatitis score, i.e., skin/ear thickness, mast cells, and serum IgE level. Finally, this suggests that our findings on the optimal ratio of PM and double emulsion‐based delivery would be beneficial in treating AD and can be applied to other allergic diseases.This article is protected by copyright. All rights reserved