Polyphenol is a kind of natural active substance with immunoregulatory activity. In this study, the immunoregulatory activities of Sargassum carpophyllum polyphenol (SCP) on the allergic reactions induced by shrimp tropomyosin were investigated. As the results, the SCP performed high hyaluronidase inhibition ability, which even greater than sodium chromoglycate (an anti-allergic medicine). SCP was able to affect the allergic reactions of RAW 264.7 macrophage cells via regulating the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase 1/2 (JNK1/2), extracellular regulated protein kinase 1/2 (Erk1/2) and p38 mitogen-activated protein kinase (MAPK) cellular signaling pathways, weakened the degranulation degree and secretion of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and histamine, and promoted the secretion of interleukin-10 (IL-10) from RBL-2H3 mast cells. In BALB/c mouse model assay, after gavage of SCP, the mouse allergic symptoms got significantly alleviated, the cytokine (IL-4, IL-10 and interferon-γ (IFN-γ)) secretion of mouse spleen lymphocytes were significantly declined and the allergic lung damage was relieved, which indicated SCP performed strong both in vitro and in vivo anti-allergic functions. Therefore, SCP could serve as candidate anti-allergic bioactive substances for shrimp induced allergy via immunoregulation.