A plethora of evidence highlights that the dysbiosis of gut microbiota is a critical factor for inflammatory bowel disease (IBD). Both in vivo and in vitro studies have demonstrated that quinoa possesses potential prebiotic effects. The present study aims to examine the potential in using quinoa to ameliorate the dysbiosis and colitis induced by dextran sodium sulfate (DSS). A total of 40 C57BL/6 mice were fed either an AIN-93M diet or a quinoa-based diet, separately. Colitis was induced for 10 animals/dietary group with a 5-days exposure to 2.5% DSS. The clinical symptoms were monitored every other day, and the gut microbiota was characterized by 16S rRNA gene sequencing. The results indicated that consumption of quinoa lessened clinical symptoms as indicated by the reduced disease activity index and the degree of histological damage (P < 0.05). As expected, the DSS treatment induced significant dysbiosis of gut microbiota in mice on an AIN-93M diet. However, compared to mice fed the AIN-93M diet, the consumption of quinoa alleviated the DSS-induced dysbiosis remarkably, as indicated by increased species richness and diversity, decreased abnormal expansion of phylum Proteobacteria, and decreased overgrowth of genera Escherichia/Shigella and Peptoclostridium (P < 0.05). The relative abundances of Firmicutes and Bacteroidetes were less altered in mice fed with quinoa comparing to those mice fed the AIN-93M diet. In summary, the consumption of quinoa suppressed the dysbiosis of gut microbiota and alleviated clinical symptoms induced by DSS, indicating the potential to utilize quinoa as a dietary approach to improve intestinal health.