In recent studies, marine macroalgae (seaweeds) have been highlighted as excellent sources of acquiring many bioactive polymers and metabolites with vast chemical and biological values, which has attracted increasing research interests in seaweeds. Among a diversity of seaweed-derived bioactive constituents, polysaccharides have been affirmed to possess an extensive array of bioactivities, such as antioxidant, antimicrobial, anticarcinogenic, immune-enhancing and anti-inflammatory activities. Due to the exhibition of these bioactivities, seaweed polysaccharides have been promised great application potential in food, feed, pharmaceutical, nutraceutical, and cosmeceutical industries. As discovered, these bioactivities were mainly contributed by the complex polymeric structural features and chemical compositions of seaweed-derived polysaccharides and were highly associated with the extraction methods. This study has comprehensively reviewed the current and prospective applications of seaweeds and their polysaccharides from nutritional and bioactive perspectives, with further shedding light on the insight into the structure-bioactivity relationship of seaweed-derived polysaccharides.