Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the small and large intestines, characterized by immunological dysregulation, overproduction of free radicals, and imbalance of gut microorganisms. Egg white protein (EWP) is being considered a promising option for treating IBD due to its antioxidant, anti-inflammatory features, and intestinal bacteria regulation. In this study, egg protein nanoparticles (EPN) were prepared to improve the stability of EWP in the gastrointestinal (GI) tract and suppress oxidative stress and regulate immune response for treating IBD. The optimization of EPN synthesis involved the processes of cold gelation methods to obtain the suitable nanosize, surface charge, and stability of EPN under various pH conditions. The obtained EPN was approximately 100 nm with a narrow distribution and stable in gastric pH condition. EPN exhibited highly antioxidant and anti-inflammatory activities via ABTS scavenging assay and lipopolysaccharide-induced RAW 264.7 macrophage cell activation, respectively. In addition, oral administration of EPN showed a therapeutic efficacy in dextran sodium sulfate-induced colitis mice by effectively suppressing lipid peroxidation, pro-inflammatory cytokine and improving colon length, disease activity index, and colonic histology. Based on the obtained results in this study, EPN is a promising protein nanomedicine for treating IBD.