Introduction: Materials and Methods: Gal EO was isolated and subjected to GC-MS for analysis. The oil components were in silico investigated against Genta-induced renal toxicity targets using network pharmacology and molecular docking approaches. In vivo studies involved the alienation of rats into four groups. The control and Genta groups rats received 0.5% CMC orally by gavage for 2 weeks and saline or Genta (100 mg/kg) I.P. injection on the 8th to the 14th day. The Genta + Gal EO (50 mg/kg) and Genta + Gal EO (100 mg/kg) groups received Gal EO (50 or 100 mg/kg, P.O.) daily for 2 weeks and Genta (100 mg/kg) I.P. injection. Renal histopathological and kidney function tests, lipid peroxidation, oxidative, inflammatory mediators, and apoptotic markers were assessed. Results: Network Pharmacology suggested Toll-like receptors 4 (TLR4) and interleukin-1beta (IL-1β) as potential targets of Gal EO components in Genta-induced renal toxicity. Gal EO significantly decreased Cr, uric acid, BUN, CysC, NGAL, and Kim-1 levels and the urine albumin/creatinine ratio. Gal EO reduced MDA and NO levels with an upsurge in the GSH content, GPx, GSH-R, catalase, and SOD levels. Gal EO lessened the gene expression of TLR4/MYD88/NF-κB/IL-1β with subsequent reduction in ICAM-1 and MCP-1 expression and the levels of MPO, TNF-α, and IL-6 while intensified IL-10. Gal EO diminished caspase 3, caspase 9, and Bax while amplified Bcl2. Conclusion: Genta-induced nephrotoxicity was mitigated by the anti-inflammatory, antioxidant, and anti-apoptotic effect of Gal EO through decreasing TLR4/MYD88/NF-κB/IL-1β signaling pathway.