Natural polysaccharides derived from renewable biomass sources are regarded as environmentally friendly and sustainable polymers. As the third most abundant biomacromolecule in nature, after proteins and nucleic acids, polysaccharides are also closely related with many different life activities. In particular, β-glucans are one of the most widely reported bioactive polysaccharides and are usually considered as biological response modifiers. Among them, β-glucans with triple-helix conformation have been the hottest and most well-researched polysaccharides at present, especially lentinan and schizophyllan, which are clinically used as cancer therapies in some Asian countries. Thus, creation of these active triple-helix polysaccharides is beneficial to the research and development of sustainable "green" biopolymers in the fields of food and life sciences. Therefore, full fundamental research of triple-helix polysaccharides is essential to discover more applications for polysaccharides. In this Review, the recent research progress of chain conformations, bioactivities, and structure-function relationships of triple-helix β-glucans is summarized. The main contents include the characterization methods of the macromolecular conformation, proof of triple helices, bioactivities, and structure-function relationships. We believe that the governments, enterprises, universities, and institutes dealing with the survival and health of human beings can expect the development of natural bioproducts in the future. Hence, a deep understanding of β-glucans with triple-helix chain conformation is necessary for application of natural medicines and biologics for a sustainable world.