Context: Citrus limon (L.) Burm.f. (Rutaceace) is a commonly available fruit variety with high medicinal and industrial values.Objective: Lemon peel (LP) extract was studied as a potent preventive and curative agent for experimentally induced hyperoxaluric rats.Materials and methods: Gas chromatography-mass spectrometry (GC-MS) analyses and toxicity study were performed for aqueous methanol LP extract. Twenty-four Wistar rats were segregated into four groups. Group 1: Control; Group 2: Urolithic (ethylene glycol (EG) - 0.75%); Group 3: Preventive study (EG + LP extract administration from 0th to 7th week); Group 4: Curative study (EG + LP extract administration from 4th to 7th week). Animals received LP extract daily by oral administration (100 mg/kg body weight) for 7 weeks.Results and discussion: GC-MS analyses revealed that compound 6 was abundant in the LP extract (32%) followed by compound 1 (∼21%). The LD50 value of LP extract was found to be >5000 mg/kg of body weight. Urolithic rats showed significantly higher urinary calcium and oxalate (4.47 ± 0.44 and 18.86 ± 0.55 mg/24 h, respectively) excretion compared with control and experimental rats. Renal function parameters like urea (84 ± 8.5 and 96.1 ± 3.6 mg/dL), creatinine (1.92 ± 0.27 and 1.52 ± 0.22 mg/dL), and urinary protein (2.03 ± 0.02 and 2.13 ± 0.16 mg/24 h) were also reduced by LP extract (p < 0.001) and corroborated with tissue analyses (SOD, catalase, and MDA levels) and histological studies in normal and experimental animals. Immunohistochemical staining of THP and NF-B in urolithic animals showed elevated expression than the control, while LP extract suppressed the expression of these proteins.Conclusion: In conclusion, lemon peel is effective in curing kidney stone disease and also can be used to prevent the disease and its recurrence. © 2015 Taylor & Francis.