This study aimed at evaluating the protective effect of long-term dietary oregano on the alleviation of carbon tetrachloride-induced oxidative stress in rats. Twenty-four female Wistar rats were allocated to four groups of six animals each. Groups 1 (control) and 2 (CCl4) were fed a basal diet, while groups 3 (oregano) and 4 (oregano + CCl4) were fed the basal diet supplemented further with ground oregano at 1% level. Following six-week feeding, the rats of groups 2 and 4 were given a single intraperitoneal injection Of CCl4 at a dose of 1 mL/kg bw. Six hours after the CCl4 injection, all animals were sacrificed, and serum, liver, kidney, and heart tissue samples were collected. Analysis results showed that the addition of oregano significantly increased the total phenolic content and the Trolox equivalent antioxidant capacity of the basal diet but had no effect on its lipid peroxidation index. Treatment with CCl4 of rats from the CCl4 group caused a significant increase in aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) in serum, whereas it decreased cholesterol and triglyceride content as compared to the control. It also increased the lipid peroxidation index and decreased the scavenging activities of the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS) radical cation, the hydroxyl anion radical, the superoxide anion radical, and the hydrogen peroxide in all tested tissues, as compared to that of the control. Without CCl4 treatment, diet supplementation with oregano had no effect on these biochemical parameters, excluding the hydroxyl radical scavenging activity, which was increased in all tested tissues as compared to that of the control. Feeding oregano before CCl4 treatment resulted in a significant decline of the increase in AST, ALT, and ALP activities (P < 0.05 vs CCl4 group), but the recorded values could not attain those of the control group (P < 0.05 vs control group). It significantly increased the reduced cholesterol and triglycerides (P < 0-05 VS CCl4 group) to values not differing from those of the control. It also resulted in a significant reduction of the increased malondialdehyde (P < 0.05 VS CCl4 group) to values that could not attain the levels of the control but had no significant effect (P > 0.05) on the reduced ABTS radical cation scavenging activity. It increased significantly the reduced hydroxyl anion radical scavenging activity (P < 0.05 vs CCl4 group) to values that could not attain those of the control in all tested tissues except kidney. Additionally, it resulted in a significant elevation of the decreased superoxide anion radical scavenging activity in serum and liver but had no effect in kidney and heart, whereas it also resulted in a significant elevation of the decreased hydrogen peroxide scavenging activity in liver, kidney, and heart but had no effect in serum. These results suggest that dietary oregano may effectively improve the impaired antioxidant status in CCl4-induced toxicity in rats.