Seaweeds and their bioactive compounds, particularly polysaccharides and phenolics can be regarded as great dietary supplements with gut health benefits and prebiotics. These components are resistant to digestion by enzymes present in the human gastrointestinal tract, also selectively stimulate the growth of beneficial gut bacteria and the production of fermentation products such as short chain fatty acids. Commonly, the health benefits of seaweed components are assessed by including them in an in vitro anaerobic fermentation system containing human fecal inocula that mimics the environment of the human large bowel. Regarding to the complex interactions between dietary components, gastrointestinal physiological processes, and gut microbiota are difficult to model in vitro. Consequently it is important to follow up the promising in vitro results with in vivo animal or human testing. The aim of this chapter is to have a comprehensive review on the application of seaweeds and seaweed-derived metabolites as prebiotics, and understand the trends, gaps and future directions of both scientific and industrial developments. This work contributes to develop and expand new platform of seaweed utilization for higher-value products, particularly to functional food and nutraceutical industries in order to serve the social demand for health awareness and support economic development.