Throughout history, man used various natural materials as a remedy for treatment of various diseases and recently witnessing a vastly growing and renewed interest in herbal medicine globally. In Palestinian folk medicine Ephedra alata and Plumbago europaea used as diuretics and for treatment of hypertension. This study aimed to evaluate the diuretic and acute toxicity effects of the aqueous extracts for these two plants in mice following oral administration. Aqueous E. alata and P. europaea extracts (500 mg/kg) were administered orally to adult mice. Urine output and electrolytes were then measured after 4 h of administration and compared with those received furosemide 10 mg/kg (positive control group) and those received normal saline (negative control group). Significant diuresis was noted in those received the aqueous extract of E. alata (p < 0.001), while the P. europaea aqueous extract had shown mild diuresis at the end of the forth hour compared to controls. Moreover, both aqueous extracts had an alkaline pH and a mild increase in the electrolyte excretion (Na, K). Our results revealed that E. alata aqueous extract has potential diuretic effect. Further studies are needed to evaluate this diuretic effect in the relief of diseases characterized by volume overload.