Marjoram (Origanum majorana L.) infusion has been used as folk medicine against depression and anxiety. However, no studies have been carried out yet to prove those activities scientifically. In this study, the anxiolytic, antidepressant-like effects, and memory impact of the hydro-ethanolic extracts of marjoram were evaluated in mice. The hydro-ethanolic extracts (250 and 500 mg/kg) were evaluated for their central nervous effect using six different behavioral tests such as light–dark box (LDB) and open field (OF) for anxiety, forced swim test (FST), and tail suspension test (TST) for depression, and object recognition test (ORT), Morris water maze (MWM) for the impact on memory. The experiments were realized on days 1, 7, 14, and 21 of treatments and compared with bromazepam for anxiety (1 mg/kg) and paroxetine for depression (11.5 mg/kg). The phytochemical screening was performed by HPLC, and the acute and sub-acute toxicities were performed following OCED guidelines (N°423 and 407) with biochemical parameters evaluation and histopathological analysis. Oral administration of marjoram hydro-ethanolic extract induced significant anxiolytic and antidepressant-like effects without memory impairment, increasing the exploration and time spent in the light area in the LDB test in a similar way to that of bromazepam. In the FST and TST, the extract was as effective as paroxetine (11.5 mg/kg, p.o.) in reducing immobility. The phytochemical screening showed the presence of ferulic acid, naringin, hydroxytyrosol, geraniol, and quercetin. This study approves the traditional use of this plant and encourages further investigation on its bioactive compounds
