This study investigated the hepatoprotective potential of Harungana madagascariensis (HM) extract against sub chronic toxicity induced by 2,2-dichlorovinyl dimethyl phosphate (DDVP) in Wistar albino rats. Wistar albino rats were randomly assigned to five groups of Eight (8) rats each; control (group 1), ‘DDVP exposed’ alone (group 2), and treatment groups (groups 3, 4, 5 ‘DDVP exposed’ + 50 mg/kg, 100 mg/kg, 150 mg/kg H. madagascariensis extract, respectively). The study spanned for 30 days, during which the male rats were treated with DDVP (10 mg/kg b.w) except for the positive control while organ weights (liver, kidney, heart, testes/epididymis), serum liver enzyme biomarkers (ALP, AST, ALT, total bilirubin, total protein), and percentage weight gain were assessed at the end of the study. The negative control group exhibited significant reductions in organ weights, elevated liver enzyme biomarkers, and decreased weight gain, indicative of DDVP-induced hepatotoxicity. The treatment groups demonstrated varying degrees of recovery in organ weights and serum biomarkers, with higher doses of HM extract showing more pronounced effects. H. madagascariensis extract exhibited hepatoprotective potential against sub-chronic DDVP-induced toxicity, as evidenced by improvements in organ weights, serum biomarkers, and weight gain. The observed dose-dependent responses highlighted the significance of HM as a potential therapeutic agent in achieving optimal hepatoprotection. These findings contribute to the understanding of natural remedies like plant-based supplements for control of pesticide-induced toxicity with HM having suggestive evidence of therapeutic potential for treatment of liver-related disorders.