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Background and Aim: Glucocorticoids are commonly used in veterinary medicine but often cause liver changes characterized by glycogen buildup, enzyme activation, and oxidative stress, known as steroid hepatopathy. Mitoquinol mesylate (MitoQ) is a mitochondria-targeted antioxidant that has shown hepatoprotective effects in experimental models; however, its potential benefits in dogs have not yet been studied. This research aimed to assess the hepatoprotective and antioxidant effects of MitoQ in dogs with experimentally induced methylprednisolone acetate (MPA)-related steroid hepatopathy. Materials and Methods: A randomized two-period crossover study was conducted using seven healthy adult Beagle dogs. Each treatment period lasted 28 days and was separated by a 28-day washout phase. In both periods, MPA (2 mg/kg, intramuscular) was administered on day 0 to induce steroid hepatopathy. Dogs received either MitoQ (20 mg/day/dog, orally) or a placebo once daily during each treatment period according to the crossover design. Clinical monitoring was performed daily. Blood samples were collected on days 0, 7, 14, 21, and 28 to measure alanine aminotransferase (ALT), alkaline phosphatase (ALP), corticosteroid-induced alkaline phosphatase (CIAP), and gamma-glutamyl transferase (GGT) activities. Liver biopsies were obtained on days 0, 14, and 28 for histopathological and immunohistochemical evaluation, including periodic acid–Schiff (PAS) staining and α-smooth muscle actin (α-SMA) detection. Data were analyzed using repeated-measures analysis of variance, and p < 0.05 was considered statistically significant. Results: MPA administration increased ALP, CIAP, and GGT activities in both groups, confirming steroid hepatopathy. Dogs receiving MitoQ exhibited lower enzyme elevations and a quicker return toward baseline compared to placebo-treated dogs, although not all differences reached statistical significance. Histological examination showed typical glycogen-type hepatocellular vacuolation in both groups, but lesions were generally milder in the MitoQ-treated group. PAS staining confirmed glycogen accumulation, and α-SMA immunostaining indicated only mild stellate cell activation, which tended to be lower during MitoQ treatment. No clinically relevant adverse effects were observed. Conclusion: MitoQ modestly reduced biochemical and histological changes linked to MPA-induced steroid hepatopathy in dogs and may serve as a promising adjunctive hepatoprotective therapy during glucocorticoid use. Larger controlled studies with longer follow-up periods and oxidative stress biomarkers are necessary to verify these initial results. Keywords: antioxidant therapy, dogs, glucocorticoids, hepatoprotection, mitoquinol mesylate, oxidative stress, steroid hepatopathy, veterinary medicine.