Objective: The objective of this study is to evaluate the neurological, behavioral, and autonomic changes of Phyllanthus niruri in Swiss albino mice using Irwin’s method. Methods: A total of 24 mice was divided into four groups of six each (3-male, 3-female in each group). Aqueous extract of P. niruri was prepared. Based on body weight aqueous extract was given to the mice by orally through gavage tube (Group I – 300 mg/kg, Group II – 600 mg/kg, Group III – 900 mg/kg, and Group IV – 1200 mg/kg). Neuropharmacological profile is studied for each mice using Irwin’s observational test, the mice were observed for 4 h after oral administration for various behavioral, neurological, and autonomic changes at 0, 1, 2, 3, 4 h. Results: P. niruri showed negligible actions at 300 mg/kg and 600 mg/kg body weight. At 900 mg/kg and 1200 mg/kg P. niruri showed certain behavioral and neuronal changes. P. niruri increased alertness, stereotypy, restlessness, irritability/aggressiveness in behavioral profile indicating that the drug is a CNS stimulant. Furthermore, it showed mild tremors in neurological profile indicating CNS excitation. Conclusion: Aqueous extract of P. niruri at 900 mg/kg and 1200 mg/kg showed changes in behavioral profile, neurological profile, showing it as CNS stimulant properties. Since it is an observational study further research should be done to explore CNS stimulant properties in various in vivo studies.