Chronic administration of Bacopa monnieri extract exert neuroprotective potential in multiple animal models of neurodegenerative disorders such as Parkinson’s, Alzheimer’s, depression and cognitive impairments. However, its mechanism of action has remained unclear. Rotenone models of Parkinson’s disease (PD) have great potential for the investigation of PD pathology and motor and nonmotor symptoms. In this study, we evaluated the neuroprotective effect of Bacopaside I (BS-I), a major triterpenoid saponin of Bacopa monnieri extract, against rotenone induced in-vivo model of PD and explored the possible molecular mechanism for therapeutic perspective. Rats were exposed to rotenone (2mg/kg body weight) for a period of 4 consecutive weeks to induce PD-like behavior. Oral treatment of BS-I (5, 15, 45 mg/kg, treated group) were started during the weeks. The behavioral data (Rotarod, foot printing and grip strength test) suggest an indication that BS-I compound plays significant role in attenuating the motor function deficit. Exposure of rotenone reduces the dopamine level and increases the oxidative stress while BS-I treatment recovers this. Furthermore, chronic administration of BS-I elevated expression levels of Dopamine transporter (DAT), Vesicular monoamine transporter (VMAT) genes and numbers of Tyrosine Hydroxylase (TH) positive neurons as compared to rotenone exposed animals. This research may help to elucidate the neuroprotective effect of Bacopaside and indicated that natural saponins target the molecular signaling pathway, which may offer new therapeutic research avenues to discover novel treatments for PD.