In our previous study, a polyphenol-utilization targeted quinoa product was developed via solid-state fermentation with Monascus anka. In this study, we investigated the polyphenol-related novel functions of the fermented product further. Compared with unfermented quinoa, M. anka fermented quinoa alleviated the trapping effect of the macromolecules, especially in the colonic fermentation stage, resulting in enhanced polyphenol bioaccessibility. Lachnoclostridium, Megasphaera, Megamonas, Dialister, and Phascolarctobacterium might contribute to polyphenol liberation and metabolism in fermented quinoa. Additionally, fermented quinoa polyphenols presented an efficient anti-obesity effect by enhancing hepatic antioxidant enzyme activities, suppressing fatty acid synthesis, accelerating fatty acid oxidation, and improving bile acid synthesis. Moreover, fermented quinoa polyphenol supplementation alleviated gut microbiota disorder induced by a high-fat diet, resulting in a decreased ratio of Firmicutes/Bacteroidota, and increased relative abundances of Lactobacillus and Lachnoclostridium. The obtained results suggested that the principal anti-obesity effect of fermented quinoa polyphenols might act through the AMPK/PPARα/CPT-1 pathway. In conclusion, M. anka solid-state fermentation effectively enhanced the bioaccessibility of quinoa, and the fermented quinoa polyphenols showed considerable anti-obesity effect. Our findings provide new perspectives for the development of dietary polyphenol-based satiety-enhancing functional foods.