The medical treatment is indicated in the development stage of Peyronie's disease (PD) for at least 1 year after diagnosis and whenever in case of penile pain. This research was conducted to demonstrate the possible effectiveness of vitamin E in PD treatment, whereas in the scientific literature this topic is much discussed. A total of 70 patients (age:26–69 years, mean: 54.1 ± 9.71) diagnosed with PD were enrolled in a conservative treatment. In addition to medical histories and physical examinations all patients underwent the following tests: International Index of Erectile Function (IIEF) questionnaire, penile ultrasound and photographic documentation, pain evaluation by a conventional 10-point pain scale Visual analogue pain scale (VAS). All 70 patients were divided into two different treatment groups: A and B, with different combinations of drugs: A = vitamin E + verapamil (injection + iontophoresis) + blueberries + propolis + topical diclofenac; B = verapamil (injection + iontophoresis) + blueberries + propolis + topical diclofenac. All patients were treated for 6 months after which they underwent the same follow-up tests as performed prior to the treatment. Intergroup analysis revealed statistically significant differences: in the vitamin E group the effective plaque size reduction was −50.2% whereas in the control group the reduction was −35.8% (p = 0.027). In group A the improvement of curvature occurred in 96.6% of the cases whereas in the control group B this occurred in 48.4% (p = 0.0001), moreover, the mean curvature decrease was respectively −12.25° and −6.73° (p = 0.01). IIEF score was significantly improved in group A patients with comorbidities and erectile dysfunction (p = 0.025). Increase in plaque size occurred only in the control group (17.1%) (p = 0.032). We can affirm that vitamin E can help to prevent the progression of PD. This study strongly supports the recommendation that the best approach for treating PD is multimodal therapy.