Plumbagin, a hydroxy-1,4-naphthoquinone, has anti-inflammatory and antioxidant properties that provide neuroprotection. The current investigation intended to determine the impact of plumbagin on behavioural and cognitive impairments in male Wistar rats caused by intrahippocampal quinolinic acid (QA) administration utilizing stereotaxic apparatus, and additionally to elucidate the underlying mechanisms. QA i.c.v. (300nM/4μl in Normal saline) was injected into the hippocampus. When QA was administered, subjects showed signs of depression (forced swim test, tail suspension test), anxiety (open field test, elevated plus maze), and anhedonia (sucrose preference test). Additionally, in the hippocampal region of QA-treated rats compared to normal control, oxido-nitrosative stress (increased nitrite content, lipid peroxidation, with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were noted. Ten and twenty mg/kg of plumbagin; Rats given QA for 21 days showed a significant improvement in their behavioural and memory deficits when treated with plumbagin (10 and 20 mg/kg; p.o.). In addition, the hippocampal MDA and nitrite levels were lowered and the GSH level was raised following plumbagin administration. Moreover, plumbagin therapy was reported to improve mitochondrial impairment and QA-induced cholinergic dysfunction (AChE). To sum up, our findings indicated that plumbagin has the potential to function as a neuroprotective medication that could be an effective means to treat chronic neurobehavioral abnormalities caused due to neurodegeneration.