Abstract Most allergic reactions are induced by mast cell activation. Mast cells play vital roles in the pathogenesis of allergic diseases. Bisdemethoxycurcumin (BDMC), a natural curcuminoid, has potential anti-allergic effects. Hence, we explored the effect of BDMC on mast cell-mediated allergic diseases. The study proved that BDMC suppresses β-hexosaminidase release, granule release, and membrane ruffling in monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukaemia cells (RBL-2H3 cells), and BDMC suppressed ovalbumin (OVA)-induced allergic rhinitis (AR) symptoms and OVA-specific IgE levels in AR mice. Furthermore, BDMC increased the survival of compound 48/80 anaphylaxis shock mice and elevated the decreased rectal temperature in OVA-induced active systemic anaphylaxis mice. These findings indicate that BDMC regulates the degranulation of mast cells, demonstrating its potential in the treatment of mast cell-induced allergic reactions. Graphical abstract Unlabelled Image Highlights • BDMC inhibits the degranulation of DNP-IgE/HSA stimulated RBL-2H3 cells. • BDMC suppresses OVA induced allergic rhinitis (AR) symptom. • BDMC increases survival of compound 48/80 anaphylaxis shock mice. • BDMC elevates the decreased rectal temperature in OVA induced active system anaphylaxis mice. [ABSTRACT FROM AUTHOR]