This is a non-randomized, open-label, prospective single-arm interventional multicentric study conducted between 2021 and 2022 at three different centers situated in Pune, India. It was conducted to evaluate the efficacy and safety of the Sitcom ® tablet (Euphorbia prostrata 100 mg) once daily and Sitcom ® cream (Euphorbia prostrata 1%w/w) for 14 days in hemorrhoids during pregnancy. The endpoints were to assess hemorrhoidal symptoms relief during the follow-up periods (one, two, four, and eight weeks and 30 days postpartum), relapse of symptoms, improvement in the disease condition at week two and 30 days postpartum, and adverse events. A total of 100 patients (mean age 24.1 years) were included; the majority (71.0%) had mild per-rectal bleeding, 69.0% with mild itching and 46.0% with moderate pain during defecation. The mean score of per-rectal bleeding and pain at defecation showed a significant reduction at each visit (86.6% and 49.3% (two weeks), 95.3% and 59.9% (four weeks), and 100% and 77.6% (eight weeks)). The mean pain score at defecation, itching, exudates, and swelling showed a significant reduction of 77.6%, 96.9%, 100%, and 84.5% at eight weeks (p<0.001). After two weeks and post postpartum follow-up, >90% and 100% good to excellent overall improvement in the disease condition were noted, respectively. No adverse events in the mother or newborn were noted. This pivotal study underscores the potential of a combination therapy with Euphorbia prostrate 100 mg tablet and cream 1% as a potential solution for managing the distressing burden of hemorrhoids in pregnant women. Furthermore, these observations will empower clinicians in the judicious selection of the most suitable course of action for hemorrhoid management during pregnancy.