The current study evaluated the sedative and anxiolytic activity of methanol extract of Nerium oleander (Family: Apocynaceae) leaves alongside with its phytochemical screening. Preliminary phytochemical screening revealed the presence of reducing sugar, tannin, glycoside, flavonoids, alkaloids, gum and protien. The methanol extract of Nerium oleander (MENO) was evaluated for sedative activity using the mice model open field test and hole cross test. The effect of MENO on central nervous system (CNS) for anxiolytic activity was determined by light/dark Box, elevated plus maze test and whole board test using swiss albino mice as experimental animal. The MENO showed significant (p<0.05) sedative effect at the doses of 200 and 400 mg/kg body weight in Open field test and Hole cross test. The present study demonstrated that MENO showed significant (p<0.05) anxiolytic effect at the doses of 200 and 400 mg/kg body weight in light-dark box test and elevated plus maze test. The movement of mice decreased significantly in hole-board test after the administration of MENO at doses of 200 and 400 mg/kg body weight, which indicates the potential anxiolytic activity. The present study indicates that the MENO possesses sedative and anxiolytic activity which trend to justify its use as traditional medicine. So, the plant may be further subjected to chemical investigation to isolate and purify the bioactive compound(s) responsible for its pharmacological activity.