Background <p>The liver is highly susceptible to toxins, such as pesticides, including rotenone, which induce oxidative stress, inflammation, and hepatocellular injury. D-carvone, a naturally occurring monoterpenoid, exhibits strong antioxidant properties. This study evaluated the hepatoprotective potential of D-carvone against rotenone-induced hepatotoxicity in Swiss albino mice.</p> Methods <p>Mice were randomly divided into four groups (<i>n</i> = 6): normal control, rotenone (RT), D-carvone + rotenone (DC + RT), and D-carvone (DC) only (<i>n</i> = 6 per group). Liver function was assessed using biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, total protein, and albumin), oxidative stress biomarkers (lipid peroxidation (LPO), catalase (CAT), reduced glutathione (GSH), and glutathione S-transferase (GST)), and histopathological evaluation of liver tissue.</p> Results <p>RT administration caused marked hepatic dysfunction, as evidenced by significant elevations in ALT, AST, ALP, and bilirubin levels, along with decreased total protein and albumin levels. Oxidative stress parameters also worsened, with increased lipid peroxidation and reduced antioxidant enzyme activity. Co-treatment with DC significantly restored liver function markers, reduced oxidative stress, and improved antioxidant defense. Histological examination further confirmed hepatoprotection, showing reduced necrosis and inflammatory cell infiltration in the DC + RT group compared to the RT-only group. DC alone did not have any adverse hepatic effects.</p> Conclusion <p>DC exerts potent hepatoprotective effects against RT-induced liver injury by reducing oxidative stress, restoring antioxidant enzyme activity, and improving histological architecture. These findings highlight the potential of this compound as a safe and natural therapeutic agent for liver disorders.</p>