Background: Tramadol is a centrally acting analgesic that is commonly prescribed for moderate and severe pain. Camel's milk is different from other ruminant milk as it is low in cholesterol, sugar and protein but high in minerals and vitamins. It also contains a high concentration of insulin and immunoglobulins. Objective: This study aimed to demonstrate the biochemical, molecular and histological, changes induced by tramadol on the rat's kidney, and evaluate the potential role of camel's milk in the attenuation of these changes. Materials and Methods: Forty adult male albino rats were equally divided into 4 groups:  Control group, tramadol hydrochloride-treated group, tramadol hydrochloride/camel's milk group, and recovery group received tramadol hydrochloride only for 4 weeks and not subjected to any others procedure for 2 weeks.  By the end of the experimental period, blood samples were collected to measure serum creatinine, urea and uric acid. Both kidneys of each rat were dissected out carefully. The right kidney was used for measurement of malondialdehyde (MDA), glutathione peroxidase (GPx) and gene expression of B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (Bax) proteins. The left kidney was preserved for histological examination. The   histological study of different experimental groups was done using hematoxylin and eosin (H & E), Masson trichrome and periodic acid Schiff (PAS) stain followed by morphometric and statistical studies. Also, electron microscopic study was done. Results: Administration of tramadol induced significant increase in plasma concentrations of urea, creatinine and uric acid as well as significant increase in MDA, as well as a significant decrease in GPx concentration. Also, the gene expression of pro-apoptotic Bax protein was significantly increased after tramadol administration. On the other hand, the gene expression of anti-apoptotic protein Bcl-2 decreased significantly compared to control group. Moreover, examination of the renal cortex of tramadol-treated group demonstrated atrophied glomerulus with collapsed tuft, wide Bowman's space, degenerated tubules, cellular infiltration and hemorrhage. Furthermore, the collagen fibers increased as well as the basement membrane thickness of the renal corpuscles. In contrast, both renal structure and function were preserved in rats treated concomitantly with both tramadol and camel milk. However, the kidney function and structure was improved to some extent at the end of recovery period of group 4. Conclusion: Camel's milk improves tramadol-induced changes in the renal function and structure of the rat's kidney.