Momordica charantia (bitter gourd) also called Karela is well-known for its medicinal qualities. The antidepressant activity of bitter gourd is least studied. All age groups are susceptible to depression, a common psychiatric illness. Antidepressants that are currently on the market have their own drawbacks. Hence, the present study was carried out with main purpose to evaluate the antidepressant activity of methanolic fruit extract of bitter gourd. Antidepressant activity of methanolic fruit extract of bitter gourd at doses of 250 mg/kg, 500 mg/kg and 750 mg/kg was evaluated in female Swiss albino mice in tail suspension test. After 1 h of dosing of distilled water as vehicle administered to normal control group (10 ml/kg, p.o.); 250 mg/kg (Group-A), 500 mg/kg (Group-B), 750 mg/kg (Group-C) methanolic extract of bitter gourd f r u i t and imipramine 15 mg/kg (positive control) was administered orally respectively, Results inferred that there was statistically significant reduction in immobility time (s) in positive control on day 7 (p<0.001) and day 14 (p<0.001). In Group-A (250 mg/kg) significant reduction in immobility time (sec) was observed on day 14 (p<0.05). However, statistically significant reduction in immobility time (s) was observed in Group-B (500 mg/kg) on day 1 (p<0.05), day 7 (p<0.05), and day 14 (p<0.01). Similarly, in Group-C (750 mg/kg) significant reduction in immobility time (s) was observed on day 1 (p<0.01), day 7 (p<0.01) , and day 14 (p<0.001). The effect of bitter gourd treatment at the dose level of 750 mg/kg was comparable with that of positive control (imipramine). In conclusion, results of the present study clearly demonstrated that methanolic fruit extract of bitter gourd exhibited antidepressant activity. Therefore, methanolic extract of bitter gourd could be considered for development natural antidepressant drugs.