In this study, 14 20 -hydroxy-40 ,60 -diisoprenyloxychalcone compounds were synthesized and their antidepressant activities were evaluated using the forced swimming test. The pharmacological results showed that six compounds significantly reduced immobility times during the forced swimming test at a dose of 10 mg/kg, indicative of antidepressant activity. Among these, three compounds (4d, 4e, and 4g) exhibited better antidepressant activity, with reduced immobility time by 38.3, 34.0, and 27.4 %, respectively. For explanation of the putative mechanism of action, compounds 4e, 4g were tested in chemical induced models.