Background: Treatment modalities for Fanconi syndrome caused by ifosfamide (IFO) are very limited. This study assessed the protective effect of lycopene (LYP) against IFO‑induced Fanconi syndrome in albino rats. Methods: Forty adult male albino rats randomized into eight groups of n = 5 were used. Group A (Control) was treated intraperitoneally (IP) with normal saline (0.2 mL), whereas groups B–D were treated orally with LYP (10, 20, and 40 mg/kg) daily for 5 days, respectively. Group E was treated IP with IFO (80 mg/kg) daily for 5 days, whereas groups F–H were pretreated orally with LYP (10, 20, and 40 mg/kg) before IP treatment with IFO (80 mg/kg) daily for 5 days. After treatment, the rats were anesthetized; blood samples were collected and evaluated for serum biochemical biomarkers. Kidneys were excised, weighed and evaluated for oxidative stress markers and histology. Results: Significant (P < 0.001) increases in serum creatinine, urea, and uric acid levels with significant (P < 0.001) decreases in glucose, phosphate, magnesium, calcium, potassium, sodium, chloride, and bicarbonate levels were observed in IFO‑treated rats when compared to control. Significant (P < 0.001) decreases occurred in kidney superoxide dismutase, catalase, glutathione (GSH), and GSH peroxidase levels with significant (P < 0.001) increases in malondialdehyde levels in IFO‑treated rats in comparison to control. Glomerulus with sclerosis, lipid accumulation, and tubular necrosis were observed in the kidneys of IFO‑treated rats. The aforementioned changes were significantly abrogated in rats pretreated with LYP 10 mg/kg (P < 0.05), 20 mg/kg (P < 0.01), and 40 mg/kg (P < 0.001) when compared to IFO‑treated rats. Conclusions: LYP may be useful as treatment for Fanconi syndrome caused by IFO.