Objective Drug-induced nephrotoxicity is a major cause of kidney injury. Aminoglycosides, like amikacin, are effective gram-negative antibiotics. However, its distinct induction of nephrotoxicity is a problematic clinical issue. This study investigated the preventive benefits of citrus bergamot extract in rats with acute renal injury caused by amikacin. Methods Five groups of six rats each received treatments for nine days: Group 1, normal control group, was gavaged DW orally. Group 2, negative control group, was gavaged DW orally plus a toxic dose of amikacin (1.2 g/kg) intraperitoneally on day 7 of the research protocol. Group 3, comparison group, was given 100 mg/kg of citrus bergamot extract. Groups (4) and (5), tested groups, gavaged citrus bergamot extract (100 and 200 mg/kg, respectively) orally and a toxic dose of amikacin (1.2 g/kg) intraperitoneally on day 7. Groups (1) and (3) administered intraperitoneal saline on day 7 to mimic the other groups. Serum, urine, tissue indicators of oxidative stress and renal histopathology were used to characterize nephrotoxicity. Results The results showed that amikacin produced nephrotoxicity by increasing the weight of the rats' kidneys and a substantial increase in the urine beta2-microglobuline as well as serum traditional biomarkers for kidney injury, urea and creatinine. Additionally, amikacin markedly raises serum cytokine levels (IL-6). Amikacin, on the other hand, significantly lowered renal antioxidant activity as measured by changes in serum malondialdehyde levels and reduced glutathione activity in this experiment. This was reinforced by the existence of significant morphological changes in the kidney. Citrus bergamot extract was able to restore renal function, accompanied by significant improvements in the aforementioned parameters of kidney function, inflammation, and oxidative stress indicators, as well as an attenuation of histopathological change. Conclusion According to biochemical and histological studies, citrus bergamot extract counteracts the detrimental effects of amikacin on renal structure and function.