Depression is a mental disorder that has become a serious global health problem with cases increasing every year, particularly among young adults. This study aimed to explore the antidepressant effect of the ethanol extract of Gynura procumbens (EEGP). In all, 20 male Balb/c mice were divided into five groups, each of which contained four mice: normal group; negative control; and extract group E1 (200-mg/kg BW), E2 (400-mg/kg BW), and E3 (600-mg/kg BW). The normal group was not given any treatment, whereas the other groups were induced using unpredictable mild stress (CUMS) for 28 days. The antidepressant activity was assessed using a forced swim test and a tail suspension test. In this study, CUMS induced changes in the weight of the mice, the emergence of abnormal behaviour, and abnormal histological features of the hippocampus. EEGP with a dose of 200-mg/kg BW to a dose of 600-mg/kg BW could reduce the duration of immobility when compared with the negative control group. EEGP possessed antidepressant activity by reducing the duration of immobility. Thus, further research is needed to understand the mechanism of action of the EEGP antidepressant activity.