Abstract: Background and Objective: Oxidative stress that may be the source of different disorders is caused by reactive oxygen species. CCl4 may cause oxidative stress. Antioxidant enzymes that are created by the body may scavenge the reactive oxygen species. The protective effects of Nicotiana plumbaginifolia (Linn) methanolic extract (NPME) against CCl4 induced oxidative damage in the kidneys and lungs of chicks were determined in this study. Materials and Methods: Two months old male Gallus gallusdomesticus chicks were subjected to this experiment. Total 36 chicks were divided into six groups i.e., Group I to VI were subjected under control, DMSO (1 mL kg–1 b.wt.), 1 mL kg–1 b.wt. CCl4 (50% in olive oil), silymarin (50 mg kg–1 b.wt.) after 24 hrs of CCl4 administration, 100 and 200 mg kg–1 b.wt. NPME after 24 hrs of CCl4 administration for three weeks. Results: The results revealed that CCl4 induced oxidative stress was more pronounced in the kidneys as compared to the lungs. CCl4 caused a significant decrease in the activity of kidney antioxidant enzymes (CAT, POD, GSH-Px) and glutathione (GSH), while an increase in the levels of TBARS, creatinine and urea than that of lungs samples. Conclusion: Since NPME treatment recovered towards normal conditions directly proportional to the dose applied and thus it was concluded that Nicotiana plumbaginifolia (Linn) methanolic extract can protect the kidneys more significantly than lungs tissues against CCl4 oxidative stress.