Background: Oral dietary supplementation is becoming increasingly popular as an addition to classical approaches for the prevention and treatment of hemorrhoidal disease. Aim: To examine the effect of orally administrated alpha lipoic acid (ALA), known for its antioxidant and anti-inflammatory properties, in the treatment of patients with permanent symptoms of hemorrhoidal disease. Methods: Patients with second- and third-degree hemorrhoids (n = 100) were enrolled into a randomized, open label, single-center trial. The study group (n = 50) was treated with 200 mg of orally administered ALA once a day during the 12-week period, the control group (n = 50) did not receive any treatment. Results: There were no significant differences in demographics, diagnosis, or exposure to major risk factors between the study and placebo group at baseline. ALA significantly improved subjective efficacy variables, such as pain and discomfort (p < 0.01) as well as objective signs of the disease, such as bleeding (p < 0.01), in comparison to the control group. Furthermore, the 3-month treatment significantly reduced the number of patients with positive C-reactive protein (CRP) value (serum CRP > 5 mg/L) from 18% before to only 2% after the treatment (χ2 = 4.65; p < 0.01). Average leukocyte count has also been significantly reduced in the treatment group (p < 0.01) from 7.29 × 10⁹/L before to 6.18 × 10⁹/L after treatment. Conclusions: The obtained results indicate that ALA is effective in the treatment of second- and third-degree hemorrhoids. Larger, double-blind controlled trials are needed to confirm the results and to investigate optimal treatment regimens.