Objectives: Hemp (Cannabis Sativa L.) has two major components: cannabidiol (CBD) and a small amount of delta-9-tetrahydrocannabinol (THC). Several studies showed the benefits of CBD and THC as an anti-oxidant, anti-histamine, and peripheral nerve activation inhibitor, which is potentially useful for treating patients with uremic pruritus. This study aims to compare the efficacy of a hemp-containing cream and a placebo in the treatment of uremic pruritus. Methods: We conducted a double-blind, randomized controlled study on hemodialysis patients with Worst Itching Intensity Numerical Rating Scale (WI-NRS) ≥ 3. Patients were randomly assigned either the hemp-containing cream or a placebo. At baseline, 2, and 4 weeks, WI-NRS and Skindex-10 scores were evaluated. The primary endpoint was the WI-NRS score at week 4. The secondary endpoints included the WI-NRS at week 2, Skindex-10 score at week 2 and 4, and the mean difference score between baseline and week 4 for WI-NRS and the Skindex-10 score. Results: A total of 60 patients were randomized. The median WI-NRS score at week 4 in the hemp group was lower compared to placebo group [3 (2-3) VS 4 (2-5), P = 0.03]. From baseline to week 4, the WI-NRS score change in the hemp group was significantly greater from the placebo group [-4 (-5 to -3) VS -2.5 (-4 to -1), P = 0.01]. The Skindex-10 score at week 4 was lower in the hemp group compared to placebo [13 (11 to 14) VS 18 (11 to 21) P = 0.048]. The Skindex-10 score change from baseline and week 4 was not significantly different between both groups. No side effects were observed in either group. Conclusions: In uremic pruritus, the topical cream containing hemp significantly reduced itching symptoms compared to the placebo.