To compare the efficacy of transdermal electromotive administration and intra-lesional injection of verapamil plus dexamethasone for the treatment of Peyronie's disease. Patients with Peyronie's disease of less than 2-year duration were randomized into two groups of transdermal electromotive administration and intra-lesional injection of verapamil plus dexamethasone. During the 6-week therapy period, a single weekly dose of 10 mg verapamil and 4 mg dexamethasone solution was administered to 30 patients in each group either by transdermal electromotive method or via the conventional injection method by a syringe connected to a 25 G needle. Evaluations of plaque length, width, and volume, penile curvature, erectile dysfunction and penile deviations were carried out before and after 1 and 3 months of the interventions. Erectile pain was reduced in the electromotive group from a mean of 5.1–1.0 in scale of 10 and from 5.4 to 3.6 in the injection group (p = 0.006). Regarding plaque length, plaque width, penile curvature plaque volume and erectile dysfunction, the electromotive administration group showed better results which, however, were not statistically significant. (p > 0.05). Transdermal electromotive drug administration yielded comparable results as against current conventional intra-lesional injection technique and fared better in controlling erectile pain.