Polysaccharides are valuable macromolecules due to their multiple bioactivities, safety, and a wide range of sources. Recently, a series of polysaccharides with antioxidant activity have been intensively reported. In this review, the latest advances in polysaccharides with antioxidant activity have been reviewed, primarily based on the investigations of polysaccharides regarding advanced extraction methods, roles in oxidative stress-related diseases, intracellular signaling pathways associated with antioxidant responses, activating pathways in the gut, structure-function relationships, and methods to improve antioxidant activity. The summarized information highlighted that much work needs to be conducted, from laboratory to industry, to understand and fully utilize the antioxidant potential of polysaccharides. Finally, future perspectives, including scaling-up of advanced extraction methods, standardizing the protocols for assessing and screening polysaccharides, bridging gaps on the biological mechanisms underlying antioxidant activity, performing clinical trials, and elucidating structureantioxidant relationships, have been addressed. The information present in this review will be helpful to the scientific community when studying on polysaccharides with antioxidant potential and provides research directions for a better understanding of the polysaccharides and promotes their successful applications in functional foods and nutraceuticals.