Essential oils of some aromatic plants provide an effective nonmedicinal option to control liver fibrosis. Mentha piperita L. essential oil (MPEO) have been reported to possess protective effects against hepatotoxicity. However, its effect against liver fibrosis remains unknown. The present study investigated the antifibrogenic potential of MPEO and its underlying mechanisms. Forty male rats divided into 4 groups were used: group 1 served as normal control, group 2 (liver fibrosis) received CCl4 (2.5 mL/kg, IP, twice weekly) for 8 weeks, group 3 concurrently received CCl4 plus MPEO (50 mg/kg, IP, daily, from the 3rd week), and group 4 received MPEO only. MPOE significantly improved the liver injury markers, lipid peroxidation (LPO), antioxidant capacity, CYP2E1 gene expressionand liver histology. Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and SMAD3 proteins. In addition, MPOE counteracted the p53 upregulation induced by CCl4 at both mRNA and protein levels. In conclusion, MPOE could effectively attenuate hepatic fibrosis mainly through improving the redox status, suppressing p53 and subsequently modulating TGF-β1 and SMAD3 protein expression. These data promote the use of MPOE as a promising approach in antifibrotic therapy.