The therapeutic potential of stigmasterol, a natural steroid alcohol with established immune-modulatory properties, was assessed on allergic cutaneous responses. We examined its suppressive effect on immunoglobulin E (IgE)-mediated active cutaneous anaphylaxis (ACA), compound 48/80 (C48/80)-induced pruritus, and irritant dermatitis induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Stigmasterol at 10-100 mg/kg significantly inhibited ACA with reduction in reaction area and concentration of the extravasated Evans blue dye. Given at 50 and 100 mg/kg, stigmasterol significantly inhibited C48/80-induced scratching behaviour when compared to saline-treated C48/80-injected control. Skin histopathology of injected sites confirmed that stigmasterol reduced mast cell trafficking and degranulation associated with C48/80-induced pruritus. Stigmasterol controlled inflammatory features such as ear skin oedema and neutrophilia and also reduced serum levels of TNFα induced by topical application of TPA. Epidermal layer thickening and inflammatory cell infiltration of ear skin tissue were significantly reduced by stigmasterol. Taken together, stigmasterol demonstrates significant potential as a molecule of interest in allergic skin disease therapy.