Twenty-nail dystrophy (TND) is a trachyonychia affecting all nails which cause aesthetic complaints. The difficulty of topical medication to penetrate through the nail plate brings a great challenge for TND treatment. We reported a case of TND in a 27-year-old woman, with clinical manifestation of trachyonychia, longitudinal ridging, mottled lunula, and subungual hyperkeratosis with ragged cuticle affected all nails. She has suffered from TND for 20 years with no systemic involvement found. Histopathological examination supported the diagnosis of nail lichen planus. The patient received a mixture of topical therapy consist of tacrolimus, urea, and salicylic acid, combined with fractional carbon dioxide (CO2) laser with pulse energy: 160 mJ, pulse duration: 8.0 ms, density level: 17, and depth level: 2. After two sessions of treatment within five weeks interval, clinical improvement was seen as refinement of nail's texture. Treatment of TND often unsatisfactory due to difficulty of drug penetration through the nail plate. The fractional CO2 laser creates a column of destruction down to the dermis, which aid penetration of topical medication and stimulate nail bed rejuvenation. The use of fractional CO2 laser as a penetration enhancer can be a therapeutic option for the treatment of TND with promising result as shown in this patient. This procedure enabled combination with topical medications as long-term therapy for TND.