The current dietary recommendations for disease prevention and management are scarce and are not well supported. Beta‐glucan or quercetin in a diet can alleviate colorectal cancer (CRC) by regulating the gut microbiota and related genes, but the effects of alternating their consumption for routine ingestion during CRC occurrence remain unknown. This study investigated the effects of alternating the consumption of β‐glucan and quercetin for routine ingestion on CRC development in mice. The mortality rate, colonic length, inflammatory cytokines, gut microbiota, and colonic epithelial gene expression in healthy and CRC mice that consumed normal and alternate diets were compared and studied. The results showed that alternating the consumption of β‐glucan and quercetin (alternating among a β‐glucan diet, a normal diet and a normal diet that was supplemented with quercetin) alleviated colon damage and reduced the mortality rate in CRC mice, with a reduction in mortality of 12.5%. Alternating the consumption of β‐glucan and quercetin significantly decreased the TNF‐α level, increased the relative abundance of Parabacteroides, and downregulated three genes ( Hmgcs2, Fabp2, and Gpt ) that are associated with inflammation and cancer. Alternating the consumption of some bioactive compounds, such as β‐glucan and quercetin, in food can contribute to human health. This experiment provided some experimental evidence for the dietary recommendations for disease prevention and management.