Background: The PADOVAN-METHOD NEUROFUNCTIONAL REORGANISATION® is a promising approach in speech therapy for treating neurodevelopmental disorders of traumatic or congenital origin. Its use is based on a long-time experience of certified therapists; however, its efficacy and safety has not yet been assessed in a systematic review. This report aims to gain evidence for the use of the therapy method. Methods: Guidelines of PRISMA, the Cochrane Collaboration Handbook, MECIR and GRADE were followed. General databases (Cochrane Library, PubMed, AWMF, Anthromedics) and additional 38 databases including grey literature were searched. Hand search was also done and experts were contacted to retrieve unpublished manuscripts. All trials investigating the effect of the method in comparison to either no intervention, alternative as state of the art or placebo intervention in English, Portuguese and German language were included. No restriction regarding study design was applied. Data related to the intervention outcome and the study method was extracted and analysed idependently. Risk of Bias was assessed using ROBINS-I for non-RCTs, adherence to CARE-Guidelines was analysed for case series or reports and keeping the Declaration of Helsinki was checked for all items. Results are presented both in evidence profiles and summary of findings tables according to GRADE. Results: Amongst 98 records assessed for eligibility, and four studies and 14 case reports were identified as appropriate for analysis with a total of n = 196 participants. Duration of reported interventions was between two days and two years. Microcephalia, down-syndrome, unspecified neurological disorders and myo-functional disorders were the main conditions of the patients with neurodevelopmental disorders. Only indirect overlapping of operationalised criteria was found; therefore conclusions are limited. Conclusion: The Padovan-Method® is a holistic therapy approach claiming feasibility to a large group of disorders making proof of efficacy difficult. An application of therapy according to the Padovan-Method® by trained therapists might be considered by clinicians (weak recommendation), and a contribution to the relief of symptoms or improvements of the conditions might be gained. Therefore, development and validation of therapy protocols and further investigation are required. PROSPERO Registration: CRD42020156124.