At the molecular level, UDCA activated PPARγ/Nrf2 antioxidative signaling while inhibiting NF-κB-mediated inflammation, and network pharmacology analysis identified 225 potential targets (including TNF-<i>α</i>, IL6, and NF-κB) within lipid/atherosclerosis pathways, collectively underscoring UDCA's multimodal protective mechanisms against NAFLD.<h4>Conclusion</h4>These findings validate UDCA's multifaceted hepatoprotection <i>via</i> microbiota-bile acid crosstalk and metabolic-inflammatory modulation. Here, NFKB1 is linked to metabolic dysfunction-associated steatotic liver disease.