IntroductionRates of neonatal opioid withdrawal syndrome (NOWS) have paralleled the rise of opioid use during pregnancy. While short-term phenotypic symptoms of NOWS are well defined, molecular implications and long-term effects are not well understood. Preferred and first-line of treatment for NOWS includes non-pharmacological interventions; however, more than half of the NOWS neonates will need pharmacologics, with opioids as the primary pharmacological treatment. While effective at reducing symptoms, treating NOWS with opioids is paradoxical given that molecular and long-term developmental consequences with such exposure are unknown. There is a pressing need for a synthesis of current and potential/ novel treatment options for NOWS.Methods and analysisFollowing a published framework, a scoping review will be conducted to evaluate NOWS treatment, including established treatment methods and novel methods that may warrant future research and consideration. Using broad search terms, as well as Medical Subject Headings terms, a comprehensive search of PubMed, Cochrane Library, Google Scholar, CINAHL, Web of Science and Scopus, as well as references of selected literature, will take place, followed by a screening procedure to identify included and excluded articles. Included studies must address NOWS treatment, or opioid withdrawal treatment of any age group, that may or may not have been tested in preclinical or clinical models. Results will summarise the current pharmacological and non-pharmacological treatment methods for NOWS, as well as potential novel treatments with a specific interest in non-opioid pharmacological interventions.Ethics and disseminationThis scoping review aims to broadly search preclinical and clinical literature as it relates to treatment of NOWS, including potential novel treatments with a specific interest in non-opioid pharmacological interventions. Given that this study does not directly involve human subjects or animal subjects research, Institutional Review Board (IRB) or Institutional Animal Care and Use Committee (IACUC) approval is not required. Results of this scoping review will be disseminated at conferences and submitted for publication in a peer-reviewed journal.