Problem statement: At present, the prevalence of neuropsychological disorders particularly anxiety, depression and dementia are increase. Many strategies have been developed in order to increase the efficiency of treatment and decrease side effects. Oxidative stress has been reported to play an important role on various path physiological states. Quercetin is a flavonoid commonly found in fruits and vegetables. It has potent antioxidant effects in vivo and in vitro. However, poor absorption, rapid metabolism and limited ability to cross the blood-brain-barrier are obstacles to its use for treatment of neuropsychological disorders. Nasal administration has been proposed as a noninvasive method to deliver bioactive substances to the brain. This route of administration has the potential of decreased hepatic metabolism and greater access to the brain tissue through the olfactory nerve compared to the oral route and could be a potential method of delivering quercetin to the CNS. Approach: This study was set up to determine the effect of quercetin liposomes via nasal administration on the anti-anxiety, anti-depression like activity and cognitive enhancing effect. In this case, Male Wistar rats were administered quercetin liposomes, containing 0.5 mg of quercetin in 20 μL (dose = 20 μg), via intranasal route once daily continually for 4 weeks. The anxiolytic activity, anti-depression like activity and cognitive enhancing effect were determined after single administration, 1-4 week of treatment using elevated plus maze test, forced swimming test and Morris water maze test respectively. Results: Quercetin liposomal encapsulation via nasal route possessed anxiolytic, anti-depression like activity and cognitive enhancing effect at all treatment duration. Conclusion: Our results demonstrated the anxiolytic, anti-depression like-activity and cognitive enhancing effect of quercetin liposomes via nasal administration and suggested that it might be used as a novel therapeutic strategy for mood disorder and cognitive deficit condition. However, further investigations about precise underlying mechanism are still required.