The pathogenesis of inflammatory bowel diseases (IBD) has not been completely understood. Nevertheless, the current hypotheses were that the intestinal homeostasis among microbiota, immune cells and intestinal epithelial cells are disrupted by multiple factors, including genetic predisposition, immune, environmental and microbiome, resulting in a dysregulated inflammation. Recent evidence suggests dietary patterns play vital roles in the disease progression of IBD, and amelioration of IBD-associated dysbiosis of gut microbiota by dietary components may help prevent and/or treat IBD. Edible seaweed, a type of marine crop rich in various macronutrients and micronutrients, confer health benefits to the host against chronic diseases, namely cancer, inflammatory disease, cardiovascular disease and obesity. Large amounts of studies have reported that components in seaweed possess protective effects against IBD and prebiotic effects on IBD-associated gut microbiota. The present study focus on the beneficial roles of seaweed bioactive compounds in IBD and IBD-associated gut microbiota dysbiosis and aims to fill the knowledge gap in the dietary prevention of IBD by seaweeds and seaweed products. Polyphenols from edible seaweed display various health benefits which have not been adequately studied. The current study aimed to characterize the composition of extractable polyphenol-rich components (EPCs) and non-extractable polyphenol-rich components (NEPCs) from three edible seaweeds (Laminaria japonica, Ulva lactuca and Porphyra tenera) and evaluate their anti-inflammatory and anti-colon cancer properties. Both EPCs and NEPCs from three edible seaweeds against lipopolysaccharides (LPS) stimulated nitric oxide in macrophages. Further mechanistic tests revealed that EPCs and NEPCs regulated the expression levels of proinflammatory enzymes, proinflammatory cytokines and antioxidant enzymes in macrophages. Furthermore, EPCs and NEPCs lowered the viability of colon cancer cells, while normal colon cells were not affected. Additionally, EPCs and NEPCs induced cellular apoptosis and led to G0/G1 cell cycle arrest in HCT116 cells. Overall, these results provide a rationale for future animal and human studies designed to examine the anti-inflammatory and chemo-preventive capacities of polyphenol-rich components from L. japonica, U. lactuca and P. tenera. Laminaria japonica (LJ) and Porphyra tenera (PT) are two major edible seaweeds with various health benefits. The current study designed to evaluate the anti-colitis properties of whole LJ and PT in dextran-sulfate-sodium (DSS)-treated mice. Supplementation of LJ and PT were found to against the loss of body weight, suppress the disease activity index (DAI), ameliorate the colonic histological injuries in colitis mice, which was linked to the reduction of the levels of pro-inflammatory cytokines and inflammatory-related proteins in the colon mucosa. Moreover, supplementation of edible seaweeds was found to alter gut microbiota diversity and composition in colitis mice. Specifically, supplementation of LJ and PT elevated the proportion of potential beneficial bacteria, such as Lactobacillus, Blautia and Roseburia, as well as lowered the relative abundance of Enterococcus, Escherichia-Shigella and Akkermansia in colitis mice. Additionally, supplementation of LJ and PT reversed the dysregulation of short-chain fatty acids (SCFAs) and bile acids (BAs) in colitis mice. Overall, these results illustrate efficacy and mechanism behind the anti-colitis effects of LJ and PT, which provide a scientific basis for the prevention of inflammatory agents.