<p>Several studies have investigated the functional properties of components derived from the brown alga <i>Sargassum macrocarpum</i>. Previously, we reported the antiallergic effects of an 80% methanol (80M) extract from the alga, harvested along the coast of Nishinoshima town, Shimane Prefecture, Japan. However, detailed information regarding the specific antiallergic compounds of this alga remain unclear. To address this gap, we conducted a study to identify the active compounds isolated from <i>S. macrocarpum</i> and to elucidate their antiallergic mechanisms. The 80M extract was dissolved in M/C (methanol:chloroform = 3:1, v/v) and three compounds were isolated using solvent partitioning and high-performance liquid chromatography. Mass spectrometry and nuclear magnetic resonance spectrometry analyses identified these compounds as meroterpenoids: sargachromenol, sargaquinoic acid, and sargathunbergol. These meroterpenoids demonstrated antiallergic properties through various mechanisms. They suppressed ear swelling in an Institute of Cancer Research (ICR) mouse model and inhibited inflammation-related enzymes, including phospholipase A₂, lipoxygenase, cyclooxygenase (COX)-2, and hyaluronidase. They exhibited anti-degranulation activity in rat basophilic leukemia (RBL)-2H3 cells. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay using RBL cells revealed that sargachromenol suppressed COX-2 mRNA expression, while sargaquinoic acid and sargathunbergol reduced the production of interleukin-6 and tumor necrosis factor-α. production. In summary, we identified three antiallergic meroterpenoids from <i>S. macrocarpum</i> and demonstrated their antiallergic mechanisms in ICR mice, which included enzymatic inhibition, anti-degranulation, and suppression of mRNA expression and cytokine production. To our knowledge, this is the first study to uncover the antiallergic properties of these three meroterpenoid from <i>S. macrocarpum</i>.</p>