Introduction: Fipronil induces vulnerable effects on the kidney causing nephrotoxicity via oxidative stress. The purpose of this study was to compare the protective effects of Uncaria tomentosa versus L-arginine against fipronil induced nephrotoxicity. Material and Methods: Thirty-six male adult rats were randomized into six groups (n=6) and received the following treatments via gavage for 42 days; group I-had distilled water, group II-Uncaria tomentosa (250 mg/kg of 20% U. tomentosa extract), group III-L-arginine (200 mg/kg of 20% L-arginine), group IV-fipronil (9.7 mg/kg; 1/10 of LD50), group V-fipronil & Uncaria tomentosa, and group VI-fipronil & L-arginine in the same doses as mentioned before. We assessed renal activities of renal malondialdehyde (MDA), total antioxidant capacity (TAC), and IL-18, as well as relative kidney weight, serum creatinine, uric acid, urea, and kidney injury molecule-1 (KIM-1). We examined the general kidney architecture, glomeruli, proximal and distal tubules, basement membranes, and collagen fibers. Ultrastructurally, the renal corpuscles and proximal tubules were evaluated by scanning and transmission electron microscopes. Results: Fipronil treatment induced a significant (P<0.05) increment in serum biochemical measures, renal MDA, IL-18, and a considerable decrease in TAC. There was a significant (P<0.05) increase in the percentage of shrunken glomeruli, basement membrane disruption, collagen degradation, and capsular adhesions. We observed ultrastructurally degenerated mitochondria and fragmented microvilli of the proximal tubules. Uncaria tomentosa and L-arginine markedly reversed the changes induced by fipronil treatment. Conclusion: It was concluded that Uncaria tomentosa and L-arginine were protective against nephrotoxicity by fipronil, the group receiving Uncaria tomentosa and fipronil provided better protection.