Water-soluble extract of beehive (WSE-BH) is a gummy semisolid bioactive content of Apis cerana indica beehive. The current experiment aimed to determine the anxiolytic, antidepressant, and anti-inflammatory activities of WSE-BH, which was extracted using distilled water. Anxiolytic and antidepressant activities were examined using elevated plus maze (EPM), hole-board test (HBT), and forced swimming test (FST), tail suspensions test (TST), respectively in Swiss albino mice (27-32 g) of both sexes. Histamine-induced paw edema were used for its anti-inflammatory activity of WSE-BH during acute inflammation induced in mice. The oral administration of WSE-BH (50 & 150 mg/kg) showed significant anxiolytic activities through time spent (30.80 and 38.19 %) and entry (47.16 and 53.89 %) in the open arm of EPM. In HBT, only 150 mg/kg exhibited a significant mean number of head dipping (7.53 times/min; P < 0.01) vs. diazepam (12.87 times/min; P < 0.001). In FST and TST, both 50 and 150 mg/kg exhibited a significant (P < 0.0001) reduction in immobility comparable to imipramine hydrochloride. WSE-BH produced a significant inhibition of histamine-induced paw edema starting at 60 min time point, with a maximal percentage of inhibition (80.12%) achieved with a dose of 150 mg/kg at 180 min time point. The current results suggested that WSE-BH has promising anxiolytic, antidepressant, and anti-inflammatory activities.