The regulatory effect of β‐eudesmol, which is an active constituent of Pyeongwee‐San (KMP6), is evaluated for allergic reactions induced by mast cell degranulation. Phorbol 12‐myristate 13‐acetate (PMA) plus calcium ionophore A23187‐stimulated human mast cell line, HMC‐1 cells, and compound 48/80‐stimulated rat peritoneal mast cells (RPMCs) are used as the in vitro models; mice models of systemic anaphylaxis, ear swelling, and IgE‐dependent passive cutaneous anaphylaxis (PCA) are used as the in vivo allergic models. The results demonstrate that β‐eudesmol suppressed the histamine and tryptase releases from the PMA plus calcium ionophore A23187‐stimulated HMC‐1 cells. β‐eudesmol inhibits the expression and activity of histidine decarboxylase in the activated HMC‐1 cells. In addition, β‐eudesmol inhibits the levels of histamine and tryptase released from the compound 48/80‐stimulated RPMCs. Furthermore, β‐eudesmol decreases the intracellular calcium level in the activated RPMCs. β‐eudesmol also decreases the compound 48/80‐induced mortality and ear swelling response. β‐eudesmol suppresses the serum levels of histamine, IgE, interleukin (IL)‐1β, IL‐4, IL‐5, IL‐6, IL‐13, and vascular endothelial growth factor (VEGF) under PCA mice as well as PCA reactions. Therefore, the results from this study indicate the potential of β‐eudesmol as an anti‐allergic drug with respect to its pharmacological properties against mast cell‐mediated allergic reactions.