The development of ulcerative colitis (UC) is closely associated with dysregulation of the gut microbiota. Polysaccharides, recognized for their prebiotic and dietary supplement properties, are increasingly utilized for UC prevention and management. In this study, Atractylodes macrocephala polysaccharides 1 (AMP 1) were successfully isolated and purified from A. macrocephala Koidz. However, the therapeutic potential of AMP 1 in UC remains underexplored. This research investigates the effects of AMP 1 on UC in mice, with a focus on its modulation of the gut microbiota and IL-17RA signaling pathway. Our findings demonstrate that AMP 1 mitigates UC symptoms in a dose-dependent manner. Notably, AMP 1 was ineffective in UC mice treated with antibiotics (ABX). However, fecal microbiota transplantation (FMT) from AMP 1-treated mice to ABX-pretreated mice restored its therapeutic effects. Further analysis suggests that AMP 1’s protective effects may be mediated through the downregulation of the IL-17RA signaling pathway. Interestingly, inhibition of the Il17ra gene ameliorated intestinal barrier damage, whereas AMP1 did not confer any significant additional effect under these conditions. These results collectively indicate that AMP 1 exerts protective effects against UC by modulating the gut microbiota and IL-17RA signaling pathway. In conclusion, AMP 1 shows promise as a potential functional food for UC management.