Citrullus colocynthis (CC) has traditionally been used in Africa, Asia, and Europe for a number of reasons. Citrullus colocynthis has been utilised in a number of polyherbal and monoherbal formulations in the Ayurvedic medical system to treat Kamp-vaat (Parkinson's illness). The goal of the research was to evaluate how well Tacrine-induced catalepy, hypolocomotion, and other biochemical changes were protected against by Citrullus colocynthis root methanolic extracts. Materials and Procedures The percolation method was used to create a methanolic extract of Citrullus colocynthis root. Tacrine (2.5 mg/kg, i.p.) was administered to cause orofacial dyskinesia and hypolocomotion, and the quantity of vacuous chewing movements (VCM), orofacial bursts (OB), and locomotor activity were quantified. All of the rats were monitored for Tacrine-induced catalepsy over the course of 1 to 5 days.Free radical scavenging activity was measured using the ABTS + assay. Methanolic extract affected the forebrain's superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH), and lipid peroxidation (LPO) inhibition. Results: During the investigation, root ethanolic extract significantly decreased vacuous chewing movements, other motor manifestations including hypolocomotion, and catalepsy. It also significantly enhanced locomotion and rearing in the open-field test. Additionally, the root extract's capacity to scavenge free radicals was dosedependent. The antioxidant action of plant extract is shown by increases in GSH and antioxidant enzymes like SOD and CAT. Our findings are in line with the usage of Citrullus colocynthis root extract for Parkinson's disease treatment that has been used traditionally.