This study aimed to assess the renal protective efficacy of the Copper II albumin Complex (Cu-II-Album Complex) compound against aflatoxin-B1 (AFB1) in rats. Forty adult male albino rats were divided into four groups (10 rats/group): group-1 served as a negative control, the remaining groups received an oral dose of (50µg/kg) of the AFB1 daily for 3-weeks according to the following protocol: one group did not receive any treatment (group-2), while the remaining two groups received 0.05g/kg of Cu-II-Album Complex either every other day (group-3) or intoxicated with AFB1 for 3-weeks then treated daily with Cu-II-Album Complex for another 3-weeks. Serum urea and creatinine, renal histopathology, indicators of kidney repair, nuclear factor-κB (NF-κB), antioxidant gene inducer (nuclear factor erythroid-2; Nrf2), and metabolic homeostasis indicator (peroxisome proliferator-activated receptor-gamma; PPARγ) were evaluated. The Cu-II-Album Complex significantly reduced serum urea, creatinine levels, and renal NF-κB and significantly increased the renal Nrf2 and PPARγ expression. The AFB1 induced renal degenerative changes were significantly reduced in the alternative treatment with Cu-II-Album Complex. In conclusion, the Cu-II-Album Complex is an effective renal protective agent against AFB1 as indicated by maintaining the renal functions and histology and upregulating the expression of the kidney antioxidant genes and renal metabolic homeostasis indicator.