Calotropis procera (Ait.) R.Br., also referred to as milkweed or ak, is a medicinalplant belonging to the Apocynaceae family, known for its medicinal properties against inflammation, pain, and neurological disorders. In this paper, the neuropsycho pharmacological (anxiolytic, antidepressant, sedative, cognitive-enhancing) and anti-inflammatory activities of ethanolic extract of Calotropis procera leaves (CPEE) are examined. The extract was analyzed phytochemically and quantitatively (phenolic and flavonoid content), thentested inrodent models. Mice were administered oraldoses ofCPEE (50, 100, and 200 mg/kg), and the following behavioral tests were performed: open field, elevated plus maze (EPM), light-dark box, forced swim (FST), tail suspension (TST),rotarod, and passive avoidance. Anti-inflammatory activity was tested with carrageenan- induced paw edema, formalin-induced licking of the paw, and in vitro COX inhibitory activity. CPEE exhibited marked dose-dependent anxiolytic and antidepressant-like activity, enhance dcognition, and possessedpotent anti-inflammatory activity equivalent to diclofenac. Phytochemical analysis yielded flavonoids, phenolics, saponins, and cardiac glycosides, and safety was assured in acute toxicity. Results substantiate the ethnomedical usage of C.procera and to emphasize its potential as a source of new neuroprotective and anti- inflammatory agents.