To clarify the nutritional mechanisms of quercetin mitigation in the digestive and absorptive functions in rats fed protein-oxidized soybean meal, 48 three-week-old male SD rats were randomly allocated into a 2 × 2 factorial design with two soybean meal types (fresh soybean meal or protein-oxidized soybean meal) and two quercetin levels (0 or 400 mg/kg) for a 28-day feeding trial. The protein-oxidized soybean meal treatment decreased (p < 0.05) the relative weights of the pancreas, stomach, and cecum, duodenal villus height, pancreatic and jejunal lipase activities, apparent ileal digestibility of amino acids, and apparent total tract digestibility of dry matter, crude protein, and ether extract. The supplementation of quercetin in the protein-oxidized soybean meal diet reversed (p < 0.05) the decreases in the duodenal length, ileal villus height, lipase activity, apparent ileal digestibility of amino acids, and apparent total tract digestibility of dry matter, crude protein, and ether extract. Transcriptomics revealed that the “alanine transport” and “lipid digestion and absorption” pathways were downregulated by the protein-oxidized soybean meal compared with fresh soybean meal, while the “basic amino acid transmembrane transporter activity” and “lipid digestion and absorption” pathways were upregulated by the quercetin supplementation. Microbiomics revealed that the protein-oxidized soybean meal increased the protein-degrading and inflammation-triggering bacteria in the cecum, while the relative abundances of beneficial bacteria were elevated by the quercetin supplementation.