ABSTRACT: The present study was undertaken to evaluate the neuroprotective potential of Maerua oblong folia leaf extract in scopolamine-induced cognitive impairment in Wistar rats. Memory and learning performance were assessed using standard behavioral paradigms such as Morris Water Maze, Elevated Plus Maze, and Y-Maze. Biochemical estimations were carried out to evaluate oxidative stress and cholinergic function by measuring acetyl cholinesterase (AChE) activity, lipid peroxidation (MDA), and antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Scopolamine administration produced significant cognitive deficits characterized by increased escape latency, increased transfer latency, and reduced spontaneous alternation behavior, confirming successful induction of memory impairment. Biochemical analysis revealed elevated AChE activity and MDA levels, along with a significant reduction in endogenous antioxidant enzymes (SOD, CAT, and GSH), indicating enhanced oxidative stress and cholinergic dysfunction. Treatment with Maerua oblongifolia leaf extract showed a dose-dependent improvement in both behavioral and biochemical parameters. The high-dose group demonstrated significant restoration of learning and memory functions, along with normalization of antioxidant status and reduction in AChE and MDA levels, with effects comparable to the standard drug Donepezil. The study concludes that Maerua oblongifolia possesses significant neuroprotective and memory-enhancing activity, possibly mediated through cholinesterase inhibition and antioxidant mechanisms. These findings suggest its potential therapeutic application in the management of neurodegenerative disorders such as Alzheimer’s disease, warranting further detailed pharmacological and clinical investigations.