Hemorrhoids complaint is one of the most common problems in most society, especially in Asian countries. Current drug treatment protocols cannot cure the disease, and they are palliative. According to Persian traditional medicine, Commiphora Mukul (CM) resin is a medication choice.AIM: This randomized study was undertaken to evaluate the efficacy and safety of crude CM resin compared to a combination of lactolose and anti-hemorrhoid (LandA) in patients with uncomplicated hemorrhoids grade 1 and 2. This trial was carried out on 99 patients with hemorrhoids, in Ghaem and Imam Reaza Hospitals of the Mashhad University of Medical Sciences, Iran. They randomly received CM 3 g/d for 4 weeks (as study group) or LandA (Lactolose syrup in laxative dose for 1 month and anti-hemorrhoid suppository daily for 10 days) as control group. Subjective and objectives variables including painful defecation, flatulence, constipation, gastro-esophageal reflux (GER), dyspepsia, proctorrhagia, anal protrusion, and colonoscopic grading were assessed before, immediately after, and 4 weeks after the treatment period. An intent-to-treat analysis was used. Safety was assessed with evaluation of clinical adverse effects by common toxicity criteria version 4.0. Forty-nine patients were assigned randomly to receive LandA and 50 to receive CM. After 4 weeks, flatulence, dyspepsia, GER, and colonoscopic grading scores significantly decreased in study group, whereas in control group constipation, painful defecation, and proctorrhagia showed better but not significant improvement. After 4-weak follow-up, the rate of constipation, and proctorrhagia also showed significantly improvement in study group. Constipation and proctorrhagia in control group recurred significantly in 4-week follow-up than after the treatment, whereas this recurrence in test group was not seen. CM was more effective than LandA in 4-week treatment of patients with uncomplicated hemorrhoids grade 1 and 2.