Bioactive polysaccharides (PS), especially the beta-glucan, commonly identified in plants, edible mushrooms, yeasts and bacteria, show a variety of beneficial effects on anti-obsogenicity, anti- diabetes, anti-inflammation, anti-infections, anti-oxidative stress, anti-allergy, enhancing immunity and anti-cancers. Besides, these PS are basically reckoned as being safe and showed little or no adverse effect towards human health. Thus many PS from mushrooms may generally have the potential of being used as prebiotics for health enhancement. As obsogenicity has becoming a global health issue, to further validate to what extent and mechanisms these mushroom PS may ameliorate obesity in animals and humans will be an essential issue. Also, it is important to know whether the amelioration of many inflammation-related diseases by PS may be achieved through regulation of overlapping inflammatory and immune pathways remains to be further addressed. Understanding the underlying biochemical signaling aspects of mushroom PS will provide valuable insights into their potential at preventing and even treating the obesogenicity and metabolic syndromes.