In the view of failure of conventional treatment modalities used for multiple reluctant viral warts to achieve satisfactory results, new treatment modalities are needed. Recently, photodynamic therapy demonstrated its efficacy and safety for such indication especially when combined with nanotechnology which maximize its benefits. In this case report, photodynamic therapy treated with PDT mediated by transfersomal Methylene blue (TMB) gel was used for treatment of bilateral multiple reluctant plane warts in the dorsum of feet in a 53-year-old woman. After two treatment session applied for her right foot, complete healing was achieved. Surprisingly, the left foot showed great spontaneous improvement without receiving any treatment. The patient was followed up for one year and did not show any signs of recurrence. This case not only highlights the ability of PDT to treat multiple reluctant plane warts but also focus on its ability to boost immune response and help body to eradicate viral infection.