Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders with a prevalence of one in 4,000 people worldwide, associated with many neurological comorbidities, such as headache. Despite the high prevalence of headache in this population, little data exist regarding the classification of headaches experienced by patients with NF1. Aim of this study is to verify the efficacy and safety of a nutraceutical complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for prophylaxis in a sample of children affected by NF1 presenting migraine without aura. Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex was orally administered twice a day for 6 months, to 18 school-aged patients with NF1 and presenting symptoms of migraine without aura (10 M, mean age 8.4 ± 1.65). Each patient kept a journal to record: number, intensity (according VAS scale), duration of attacks and concomitant symptoms. In addition, the PedMIDAS scale was administered to assess migraine-related disability. To verify the efficacy of the association, we tested the starting frequency (T0) of headache after 6 months (T1) and then we calculated the migraine frequency delta percentage to express the decrease in monthly frequency. After treatment, a reduction was reported (p < 0.001) in all migraine outcomes (frequency, duration, intensity, and grade of disability). In conclusion, the present study should be considered as the first report on the efficacy and safety of nutraceutical complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for the prophylaxis of migraine in children affected by NF1. Our findings suggest that headache symptoms should be considered a therapeutic target independent of primary disorder.