The current study was performed to investigate the toxic effects of aflatoxin B1 (AFB1) through the evaluation of kidney function tests and histopathological examination of renal tissues, targeting the therapeutic role of Marjoram (Origanum vulgare essential oil-OEO) in improving health status. Forty-eight New Zealand Whites growing rabbits (four weeks old) weighing on average660.5 ± 2.33 g were randomly and equally distributed into four groups, each of which had four replicas of three animals as the following: Control group (only basal diet), AFB1 group (0.3 mgAFB1/kg diet), OEO group (1 g OEO/kg diet) and co-exposed group (1 g OEO/kg + 0.3 mg AF/kg diet). Our study lasted eight weeks and was completed at 12 weeks of age. The results revealed that OEO decreased the toxic effects of AFB1 in rabbit kidneys by substantially reducing the cystatin C levels in the AFB1 group. Additionally, OEO decreased oxidative stress and lipid peroxidation levels in the co-exposed group. Moreover, OEO reduced DNA damage and inflammatory response in addition to the down-regulation of stress and inflammatory cytokines-encoding genes. Besides, OEO preserved the cytoarchitecture of rabbits’ kidneys treated with AFB1. In conclusion, O. vulgare essential oil supplementation ameliorated the deleterious effects of AFB1 on the rabbits’ kidneys by raising antioxidant levels, decreasing inflammation, and reversing oxidative DNA damage.