The plant Cissus tuberosa Moc is abundant in phenolics, has been documented to have neuroprotective properties. The study seeks to determine the neuroprotective effects of C. tuberosa ethanolic extract (CTE) against Parkinson’s disease by evaluating its impact on motor dysfunction, cognitive deficits, neuroinflammation, and neurodegeneration in paraquat-induced Parkinson’s disease models. The research hypothesizes that CTE can modulate key biomarkers involved in Parkinson’s pathology, including α-synuclein, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), assessed through qRT-PCR, as well as interleukin-6 (IL-6) and TNF-α, evaluated through ELISA. Parkinson disease was induced by using paraquat intraperitoneally. The study was designed by considering various groups with their respective treatments, control group treated normally, disease control receiving paraquat (1 mg/kg, i.p.), standard treated grabbed with (levodopa+carbidopa), and three treatment groups received plant extract (150, 300, 600 mg/kg) respectively for 21 days study period. Both behavioral, and biochemical analysis were performed. HPLC analysis revealed the presence of several phenolic compounds. CTE significantly improved motor function and cognitive performance in rats, showing a dose-dependent reduction in paraquat-induced neurotoxicity (150 < 300 < 600 mg/kg, P<0.001). CTE significantly restored antioxidant enzyme levels (P<0.001), contributing to the alleviation of oxidative stress. Neurotransmitter levels were significantly improved in a dose-dependent manner (P<0.001), while acetylcholinesterase (AChE) levels were significantly reduced (P<0.001). CTE treatment showed significant restoration of brain tissue, reducing neuroinflammation and neurodegeneration, thereby preserving normal brain structure. ELISA testing demonstrated a significant (P<0.001) downregulation of IL-6 and TNF-α levels in CTE-treated groups. qRT-PCR results showed significant downregulation of α-synuclein, IL-1β, and TNF-α mRNA expression in CTE-treated groups compared to the diseased group, suggesting neuroprotective effects. The study concludes that CTE has potential therapeutic effects in alleviating Parkinson’s disease symptoms, primarily through its antioxidant, anti-inflammatory, and neuroprotective properties.