Background <p>Scabetic nodules are a cutaneous hypersensitivity reaction to scabies mites and their byproducts, often accompanied by persistent pruritus. These nodules remain a therapeutic challenge due to the lack of effective treatments.</p> Objective <p>We sought to assess the effectiveness and tolerance of thalidomide for genital scabetic nodules.</p> Methods <p>We performed a retrospective evaluation of thalidomide treatment (50–200&#xa0;mg/day for 2–3 consecutive weeks) in 38 male patients with genital nodular scabies who had previously been infested with scabies mites and were left with persistent pruritic nodules on the genitals.</p> Results <p>A total of 38 male patients (age range: 18–40 years; mean age: 28.2 ± 5.79 years) with post scabetic nodules were included. Some of them had been refractory to other forms of therapy. Of the 38 patients, 28 patients (73.7%) showed nodule resolution after 2 weeks of treatment. A significant reduction in the number of nodules was observed at the end of the three-week treatment period (<i>P</i> &lt; 0.05), and there was no sign of relapsing. Meanwhile, after two weeks of thalidomide treatment, the patient’s pruritus symptoms significantly improved, manifested as a significant decrease in VAS (<i>P</i> &lt; 0.05), and after three weeks of treatment, VAS further significantly decreased (<i>P</i> &lt; 0.05). Infrequent adverse events, including rash, mild dizziness, and/or drowsiness, occurred in nine patients and resolved after drug withdrawal.</p> Conclusion <p>Thalidomide may be a promising option for treating refractory scabies nodules.</p> Clinical trial <p>Not applicable.</p>