This study provides a detailed histological and immunohistochemical analysis of the kidney and adrenal gland in Varanus niloticus (Nile monitor lizard), highlighting their structural features and adaptive mechanisms. Ten adult female Nile monitors were collected from Qena Province, Egypt, and their kidneys and adrenal glands were examined. Kidney tissues were processed for histological analysis, and immunohistochemistry was performed to evaluate the expression of key markers, including vimentin, E-cadherin, CK7, and NSE. In contrast to other reptiles, the kidney was divided into the cortex and medulla and contained a loop of Henle. The cortex contains renal corpuscles and nephron tubules, while the medulla primarily comprises collecting ducts. The proximal tubules were lined with acidophilic cuboidal cells, whereas the distal tubules exhibited pale cuboidal cells with fewer microvilli. Immunohistochemistry revealed vimentin expression in podocytes and a few renal tubule epithelial cells, while E-cadherin was expressed in the distal tubules, loop of Henle, and collecting ducts. NSE was strongly expressed in the renal corpuscles and macula densa of the juxtaglomerular apparatus, as well as in the peripolar cells, but was absent in the proximal tubules. CK7 was predominantly expressed in the distal tubules and collecting ducts. The adrenal glands comprise steroidogenic and chromaffin cells associated with the posterior cardinal veins of the kidney. NSE was strongly expressed in chromaffin cells, while vimentin was detected in steroidogenic cells. E-cadherin and CK7 are not expressed in the adrenal tissues. These findings provide insights into the structural and functional adaptations of the kidney and adrenal glands in Nile monitors, offering a foundation for future research into the comparative anatomy and functional ecology of reptilian excretory and endocrine systems.