This study was to investigate the effects of in vitro simulated saliva-gastrointestinal digestion on the physicochemical properties and bioactivities of okra polysaccharides (OPS). Results showed that the digestibilities of OPS were about 5.1%, 37.5%, and 41.3% after saliva digestion (SD), saliva-gastric digestion (SGD), and saliva-gastrointestinal digestion (SGID), respectively. The SGID significantly changed the physicochemical properties of OPS, such as total uronic acids, total flavonoids, monosaccharide composition, rheological properties, and molecular weights (M). Especially, M changes resulted in the breakdown of glycosidic bonds during SGD, and the degradation of OPS during SGID was mainly caused by disrupting aggregates. Furthermore, the bioactivities of OPS were also affected by SGID. After SGID, OPS still possessed strong antioxidant activities, binding capacities, and prebiotic activities, but the α-glucosidase inhibitory effect was obviously decreased. Overall, results can provide valuable and scientific support on the oral administration of OPS as functional foods and medicines in the future.