Introduction: There are currently no approved pharmacological therapies for the core symptoms of autism spectrum disorder (ASD), prompting nearly half of patients or their carers to seek complementary and alternative medicine approaches. There is now compelling clinical and basic scientific evidence that megavitamin therapy can help relieve the core symptoms of ASD, perhaps by modulating cellular energy metabolism and oxidative stress. While many patients also use homeopathic preparations, there are very little data on their efficacy. Case presentation: Based on these data and underlying rationale, a new integrative medicine approach was designed for ASD that combined parenteral B and C megavitamin therapy and a complex homeopathic preparation designed to target the core features of ASD pathobiology. The approach was tested in three young children with ASD, all of whom exhibited a significant increase in their spoken vocabulary and a noticeable improvement in interaction skills after three months of therapy. Discussion: This is only the third report of the use of a homeopathic preparation is ASD and the first report of its rational combination with megavitamins. The impressive symptom resolution and absence of side-effects seen here suggest that this integrative medicine approach is a promising intervention for children with ASD and should be further studied in larger clinical cohorts.