This study investigates the therapeutic potential of ginseng-derived nanoparticles (GDNPs) in inflammatory bowel disease (IBD). GDNPs were found to scavenge reactive oxygen species (ROS) from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, and enhance the diversity of the intestinal flora. GDNPs also stabilized the intestinal barrier, promoting tissue repair. The mechanisms of action of GDNPs were elucidated through their effects on the TLR4/MAPK and p62/Nrf2/Keap1 pathways, demonstrating anti-inflammatory and antioxidant properties. In a mouse model of IBD, GDNPs significantly reduced inflammatory factors and improved the intestinal environment, suggesting their potential as an alternative therapeutic strategy for IBD. The study highlights the therapeutic potential of GDNPs in IBD by modulating the intestinal microenvironment and maintaining homeostasis.This study investigates the therapeutic potential of ginseng-derived nanoparticles (GDNPs) in inflammatory bowel disease (IBD). GDNPs were found to scavenge reactive oxygen species (ROS) from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, and enhance the diversity of the intestinal flora. GDNPs also stabilized the intestinal barrier, promoting tissue repair. The mechanisms of action of GDNPs were elucidated through their effects on the TLR4/MAPK and p62/Nrf2/Keap1 pathways, demonstrating anti-inflammatory and antioxidant properties. In a mouse model of IBD, GDNPs significantly reduced inflammatory factors and improved the intestinal environment, suggesting their potential as an alternative therapeutic strategy for IBD. The study highlights the therapeutic potential of GDNPs in IBD by modulating the intestinal microenvironment and maintaining homeostasis.