Background Oral language skills are associated with children’s later self-regulation and academic skills; in turn, self-regulation in early childhood predicts successful functioning later in life. Yet research to date has not tested the combined benefits of interventions for oral language and self-regulation skills. Objective The primary objective of this study is to evaluate the separate and combined effectiveness of an oral language intervention (ENRICH) and a self-regulation intervention (ENGAGE) with early childhood teachers and parents for children’s oral language, self-regulation, and academic functioning. Methods The Best Start study (Kia Tīmata Pai in te reo Māori, the indigenous language of New Zealand) is a cluster randomized controlled trial with teachers and children in approximately 140 early childhood centres in New Zealand. Centres are randomly assigned to receive either oral language intervention only (ENRICH), self-regulation intervention only (ENGAGE), both interventions (ENRICH + ENGAGE), or an active control condition. Teachers’ and parents’ practices and children’s oral language and self-regulation development are assessed at baseline at age 1.5 years and at approximately 9-month intervals to age 5, and academic performance will be assessed at age 6. Teacher-child interactions will also be videotaped approximately every 9 months in a randomly selected subset of the centres. Finally, children’s brain and behavior development and interactions with their parents will be assessed approximately every 6 months to age 6 years in a sub-group of volunteers. Discussion Our previous studies show the separate benefits of oral language and self-regulation interventions with parents and educators for young children. In this study, we are investigating the separate and combined benefits of these two interventions in a large-scale cluster randomized controlled trial of teachers, parents, and young children. The results will inform theories of self-regulation development and the design of early childhood curricula. Trial registration This trial was registered with the Australian New Zealand Clinical Trial Registry (ANZCTR) as ACTRN12621000845831.