The current study sought to determine the anxiolytic, antidepressant, and anti-inflammatory properties of distilled water-soluble extract of beehive (WSE-BH). Gas chromatography–mass spectrometry (GC-MS) studies were used to characterize the chemical compositions obtained from beehives extracted in water and methanol (also fractions). The GC-MS analysis identified 19 compounds in WSE-BH, including high total phenol and flavonoid contents, compared with the methanol extract (21 compounds), ethyl acetate fraction (9 compounds), and CCl4 fraction (27 compounds). The oral administration of WSE-BH (50 and 150 mg/kg) showed significant anxiolytic activities assessed by time spent in (30.80% and 39.47%, respectively) and entry into (47.49% and 55.93%, respectively) the open arms of the elevated plus-maze (EPM). Only the 150 mg/kg dose resulted in a significant effect on the number of head-dipping events in the hole-board test (HBT) (40.2 ± 2.33; p < 0.01) vs. diazepam (64.33 ± 3.16; p < 0.001). Both the 50 and 150 mg/kg doses resulted in significant (p < 0.001) decreases in immobility in the forced swim test (FST) and tail suspensions test (TST), corresponding to the effect of fluoxetine. WSE-BH inhibited histamine-induced paw edema significantly beginning at 60 min, with the 150 mg/kg dose having the highest effect at 180 min. The current findings suggested that WSE-BH had anxiolytic, antidepressant, and anti-inflammatory properties.