The present study was designed to study the preventive effect of hydroalcoholic extract of ripe pistachio hulls (RPH) in the elevated plus maze model of anxiety. One hundred twenty female wistar rats in their estrous cycle were divided into 15 groups of 8 each and received various concentrations of hydroalcoholic extract of RPH except the control groups. Elevated plus maze was used to measure the level of anxiety. Percentage of time spent in the open arms (%OAT), percentage of the number of entries into the open arms (%OAE), locomotor activity, and time spent in the closed arms (CAT), and the number of entries in to the closed arms (CAE) were measured and compared. Dose-response experiments showed that only 10 mg/kg dose of RPH extract significantly increased %OAT (P < 0.001) and %OAE (P < 0.05) compared to the control group, indicating anti-anxiety effects of the extract. Also, pentylenetetrazol and an estrogen receptor antagonist (ERA) tamoxifen could block anti-anxiety effects of the extract (P < 0.001). It was also noticed that tamoxifen was able to significantly reduce locomotor activity. As the RPH extract showed a preventive effect in experimental model of anxiety, it might be concomitantly administered with other anxiolytic medications.