OBJECTIVE To carry out the comparative nootropic, neuroprotective potentials of two medicinal plant species. METHODS For neuroprotective activity; behavior models (elevated plus maze & morris water maze), in vivo antioxidant (superoxide dismutase, catalase, lipid peroxidation & reduced glutathione), inflammatory markers (IL-1β, IL-6 & TNF-α) and acetylcholine esterase (AChE) assessment procedures followed at different dosages i.e. 250 & 500 mg/kg of Evolvulus alsinoides and Centella asiatica ethanolic extracts. At the end of the study, it was performed histopathological analysis of the following organs: brain, heart, liver, and kidney. RESULTS In oral administration of different doses of ethanolic extracts of both medicinal plants i.e. Sco + EEA 250 = 2.49 ± 0.29 , Sco + EEA 500 = 2.67 ± 0.36, Sco + ECA 250 = 2.33 ± 0.17, Sco + ECA 500 = 2.77 ± 0.21, Sco + EEA + ECA 250 = 2.61 ± 0.32 and Sco + EEA + ECA 500 = 2.79 ± 0.16 U/mg of protein respectively against the scopolamine induced group Sco (control) = 5.51 ± 0.35 U/mg of protein extracts shows neuroprotective and nootropic activity with reducing AChE level in the brain homogenate of swiss albino mice. CONCLUSIONS Since the E. alsinoides & C. asiatica are already used in traditional Indian medicine as the neuroprotective agent and also found promising effects over inflammatory diseases, wound healing, and immunomodulatory activity. The neuroprotective effect of both plants extracts attributed to inhibition of AChE activity and improve the spatial memory formation.