The authors investigated baricitinib, a selective JAK1/JAK2 inhibitor, as a potential chronic kidney disease (CKD) treatment aimed at slowing renal fibrosis. They used network toxicology, protein–protein interaction analysis, molecular docking, and analysis of safety reports from the 2018–2024 FAERS database. They identified 229 common target proteins, with the core nodes AKT1, SRC, STAT3, EGFR and ESR1 showing high binding affinity, in some cases higher than JAK1. Pathway analysis suggested that baricitinib may affect the JAK‑STAT/MAPK and TGF‑β/Smad3 signaling pathways, which are important in renal inflammation and fibrosis. Predictive toxicology drew attention in particular to potential respiratory and acute toxic risks. 6,006 reports were analyzed from the FAERS database, where significantly increased signals for infections and thromboembolic events were found. There was no disproportionate signal for adverse renal effects in these data, supporting the need for further prospective studies focusing on the efficacy and safety of baricitinib in CKD.