Soursop consumption is beneficial to health, but there have been few clinical studies observing its benefit in human subjects. We investigated the effects of soursop supplementation on blood pressure (BP), serum uric acid (SUA), and kidney function. A total of 143 subjects were included in this randomized controlled trial. Subjects were selected from a prehypertension population dataset (n = 4190) in the “Mlati Study Database” in 2007 (using the Joint National Committee (JNC) 7 guideline). After 10 years, 143 samples showed essential prehypertension combined with high-normal SUA levels. Subjects were randomly allocated into two groups, i.e., the treatment and control group. For a 3-month period, the treatment group was given 2 × 100 g soursop fruit juice per day and the control group was not treated. Using the JNC 7 guideline, the treatment group showed a significantly lower mean systolic BP after being adjusted by three times of examinations (baseline, week 6 and 12) compared with the control group. Furthermore, the control group was more likely to have prehypertension, hypertension, and high-normal and high SUA levels after 6 weeks, as well as after 12 weeks, compared with the treatment group. An additional analysis using the 2017 ACC/AHA guideline for subjects with stage 1 hypertension showed results similar to that using the JNC 7 guideline. Moreover, it indicated that mean of both systolic and diastolic BP of the treatment group was significantly lower compared with the control group after 12 weeks of treatment. We conclude that soursop supplementation can lower BP and SUA levels.