By integrating multi-omics approaches, this study reveals a crucial connection between ferroptosis and immune microenvironment dysregulation in Crohn’s disease (CD), identifying seven hub ferroptosis-related differentially expressed genes (FEDGs): SCD, ATF4, SAT1, RPL8, MUC1, MTDH, and ATP6V1G2. This evidence concerns the gene RPL8 and Cowden disease.