Objective <p>Parkinson's disease is the second most common neurodegenerative disorder in the world. The objective is to investigate the extract's impact on motor deficits and neurochemical alterations associated with Parkinson's disease in a reserpine-induced rat model of Parkinsonism, providing insights into its therapeutic potential.</p> Methods <p>Male and female Wistar rats were randomly assigned to various groups (<i>n</i> = 6). Eight groups were established to induce a Parkinson's disease-like condition using reserpine, each treated with varying doses of <i>Euphorbia Tirucalli</i> extract and its nanosuspension. Behavioural, biochemical, and histopathological assessments were conducted 24&#xa0;h after the final administration. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s post hoc test for data interpretation.</p> Results <p>Reserpine administration resulted in reduced locomotor activity and impaired motor coordination. It also lowered catalase and Superoxide Dismutase levels while increasing lipid peroxidation compared to the normal control group. Histopathological examination revealed vacuolated cytoplasm. Treatment with levodopa, <i>Euphorbia Tirucalli</i> extract, its nanosuspension, and their combination normalized behavioural deficits, biochemical parameters, and histopathological induced by reserpine.</p> Conclusion <p>Both the nanosuspension and the extract of <i>Euphorbia Tirucalli</i> demonstrated neuroprotective effects through their antioxidant activity, effectively ameliorating behavioural deficits induced by reserpine. These findings highlight the therapeutic potential of <i>Euphorbia Tirucalli</i> extracts, suggesting their suitability for clinical application pending additional research.</p>