Hemorrhoidal disease is one of the most common gastrointestinal ailments affecting life quality of the patients. Unani classical literature is replete with anti-hemorrhoidal drugs, but scientific evidence is lacking. Therefore, Safūf Zāj (powdered alum) and Marham-e-Māzū (gall ointment) having potent anti-hemorrhoidal actions were selected to evaluate their efficacy in hemorrhoids. This clinical trial was conducted on 30 participants with hemorrhoids, aged > 18 years. All the participants received Safūf Zāj for sitz baths and Marham-e-Māzū to be applied twice daily for 2 weeks. Primary outcome measures were: change in pain intensity, anal itching, and defecate discomfort assessed on 100 mm VAS scale and per-rectal bleeding assessed on 4-point scale. Secondary outcome measures were: change in the size of the external hemorrhoidal mass assessed on 5-point scale, grade of internal hemorrhoid assessed by Goligher classification and quality of life (QoL) assessed on SF-12 questionnaire. The per-protocol analysis was done on 30 participants and statistically significant improvement was seen in primary and secondary outcome measures. Moreover, both the mental and psychological components of QoL were improved. The study inferred that therapeutic approach of Safūf Zāj and Marham-e-Mazu is safe and efficacious in hemorrhoids. Future studies with well-designed RCTs are highly recommended. Supplementary Information The online version contains supplementary material available at 10.1007/s13596-022-00634-6.