Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, following Alzheimer's disease. It is characterized by the degeneration of dopaminergic neurons in the SNpc, resulting in both motor and non-motor symptoms. Current treatments are limited, and PD's molecular basis involves alpha-synuclein aggregation, ubiquitination dysregulation, and oxidative stress. Nicotine, found in tobacco, has been associated with reduced PD risk in epidemiological studies and shown neuroprotective effects in animal models. However, its impact on oxidative stress remains unclear. A study involving 160 albino laboratory mice investigated nicotine's effects in an MPTP-induced PD model. The mice were divided into four groups: control, nicotine, MPTP, and MPTP + nicotine. The study assessed behavioral tests, dopamine levels in the SNpc, and antioxidant system activity. Nicotine improved motor function, increased dopamine levels, and reduced oxidative stress markers in the PD model. Importantly, it selectively enhanced the activity of antioxidant enzymes, superoxide dismutase, and catalase, in PD-affected mice without affecting healthy animals. It enhances the activity of key antioxidant enzymes in the substantia nigra, suggesting potential therapeutic avenues for PD treatment. However, further research is needed, including human studies and a deeper understanding of nicotine's impact on oxidative stress. These results contribute to our understanding of PD pathogenesis and offer insights into novel therapeutic approaches for this debilitating disorder. They also raise questions about the differential effects of nicotine in healthy individuals and those with PD, highlighting the need for targeted interventions in neurodegenerative diseases.