Acalypha indica has been used in poisoning cases and are known to possess significant antioxidant activities. The objective of this study is to evaluate the protective effects of an aqueous extract (5 g/l) of A. indica (leaves and stems), on biochemical disorder, oxidative stress and histopathological changes induced by muscle extract of puffer fish Lagocephalus lunaris in swiss albino mice. Mice injected with L. lunaris muscle extract (1 ml/100g body weight) for 10 days showed (1) a reduced appetite and diarrhea resulting in a lower growth rate than controls, (2) an increase in serum Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase and Total & Direct bilirubin levels suggesting liver functional disorders, (3) an increase of serum creatinine and uric acid concentrations highlighting renal insufficiency and (4) increase in the level of serum triglycerides, total cholesterol, glucose and low density lipoproteins indicate the interference in the metabolism or biosynthesis of lipids (5) an oxidative stress as evidenced by the raise of TBARS and the inhibition of antioxidant enzymes (Superoxide dismutase, Catalase and Glutathione peroxidase) activities in liver, kidney and heart tissues (6) histopathological changes in liver, kidney and heart tissues. Absorption of A. indica aqueous extract as a drink, for 10 days demonstrated ameliorative action and prevented the disorders induced by L. lunaris muscle extract. © 2013 IJDDR, Niharika Mandal et al.