Paraquat (PQ), an environmental neurotoxicant, causes acute fatal poisoning upon accidental or intentional ingestion (suicidal cases) worldwide. To date, an effective remedy for PQ toxicity is not available. In this study, we have evaluated the therapeutic efficacy of Bacopaside-I (BS-I), an active compound found in the plant extract of Bacopa monnieri (Brahmi), against acute PQ intoxication using zebrafish as a model organism. Adult zebrafish were injected with a dose of either 30 mg/kg or 50 mg/kg PQ. PQ-intoxicated zebrafish showed an increased rate of mortality and oxidative imbalance in their brain. Also, the proliferation of neural cells in the adult zebrafish brain was inhibited. However, when BS-I pretreated zebrafish were intoxicated with PQ, the toxic effects of PQ were ameliorated. PQ treatment also affected the expression of particular genes concerned with the apoptosis and dopamine signaling, which was not altered by BS-I administration. Our results highlight the efficiency of BS-I as a novel therapeutic agent for PQ intoxication. It further compels us to search and evaluate the molecular mechanisms targeted by BS-I to develop a potent therapy for acute PQ intoxication.