Background: Hepatic damage is a major cause of poor quality of living and mortality worldwide. This study investigates the hepatoprotective effects of cocoa seed extract against reserpine-induced hepatotoxicity in male Wistar rats. Methods: Thirty adult male Wistar rats were divided into six groups for a 28-day study: Group A (control), Group B (0.5 mg/kg/B.W reserpine), Group C (20 mg/kg/B.W fluoxetine), Group D (1000 mg/kg/B.W cocoa seed ethanolic extract), Group E (0.5 mg/kg/B.W reserpine + 1000 mg/kg/B.W cocoa seed ethanolic extract), and Group F (0.5 mg/kg/B.W reserpine + 20 mg/kg/B.W fluoxetine). The liver was harvested, placed in 10% neutral buffered formalin, and processed for biochemical, histological analysis. Also, liver tissues for cytokeratin-7 expression was processed according to standard immunohistochemical staining procedures. Data were analyzed using GraphPad Prism 9.0 software and one-way ANOVA. Results: There was a significant decrease in ALT, AST, and ALP levels in animals treated with cocoa extract compared to untreated animals. Meanwhile, cytokeratin expression was higher in the liver of untreated animals relative to the treated groups. Conclusion: Theobroma cacao seed extract shows potential in mitigating reserpine-induced hepatotoxicity, contributing to novel therapeutic strategies for liver disorders and providing insights into the mechanisms of cocoa seed bioactive compounds.