The present work was undertaken to evaluate the efficacy of the methanolic leaves extract of Cissus rotundifolia, as an anti-urolithic and antihypertensive agent in albino rats by measuring the biochemical parameters, enzyme immunoassay, and free radical scavenging activity using DPPH assay. Twenty four male albino rats were divided into 4 groups (n = 6) as G1 (negative control) received a normal diet, G2 (positive control) received EG (0.75%) and 1% aluminum chloride; G3 was given 200 mg/kg of CR extract daily via a gastric tube for 28 days, G4 was orally given 400 mg/kg of CR extract for 28 days. All the tested samples showed a significant antioxidant DPPH radical scavenging activity in doses of 200 and 400 mg/kg, b.w. A notifiable decrease in serum urea and creatinine levels were also, observed. The present study emphasizes the safe herbal remedies of C. rotundifolia as anti-hypertensive and antioxidants as well as anti-urolithiatic.Keywords: Cissus rotundifolia; antiurolithiatic; antihypertensive; antioxidant.