BackgroundAmerican Indian and Alaska Native (AI/AN) youth experience serious disparities in sexual and reproductive health, including the highest teen birth rate among racial/ethnic groups, and disproportionate rates of sexually transmitted infections (STI), including HIV. A growing number of evidence-based programs (EBPs) that integrate the strengths and cultural teachings of Native communities exist. Yet, multiple factors, including lack of trained personnel, limited resources, and geographic isolation, may hinder their adoption and implementation. Innovative implementation strategies that facilitate the adoption and implementation of sexual health EBPs in Native communities may help reduce these disparities.MethodsWe applied Implementation Mapping, a systematic planning framework that utilizes theory, empirical evidence, and community input, to adapt a theory-based, online decision support system, iCHAMPSS (CHoosing And Maintaining Effective Programs for Sex Education in Schools), to support underlying dissemination and implementation processes unique to Native communities. We used an iterative design process, incorporating input from Native practitioners and academicians, to ensure that the adapted decision support system reflects cultural identification, community values, and experiences.ResultsGrounded in diffusion of innovations, organizational stage theory, and social cognitive theory, the Healthy Native Youth Implementation Toolbox supports Native practitioners through five phases (Gather, Choose, Prepare, Implement, and Grow) to adopt, implement, and maintain a culturally-relevant, age-appropriate sexual health EBP. The Toolbox provides tools, ready-to-use templates, and guidance to plan, implement, and grow a culturally-relevant adolescent health program with their Tribe or community. Hosted within the Healthy Native Youth website (www.healthynativeyouth.org), the Toolbox comprises: (1) a curriculum portal with access to 15 culturally-relevant, age-appropriate evidence-based health promotion programs for AI/AN youth; (2) a “resource library” comprising 20+ support tools, templates, and links to external resources, and (3) “stories from the field” comprising testimonials from experienced Native educators, who have implemented sexual health programs.ConclusionThere is a continued need to design, test, and evaluate D&I strategies that are relevant to Native communities. The Healthy Native Youth Implementation Toolbox contributes to the dissemination and implementation of evidence-based, culturally-relevant sexual health education programs in diverse Native communities. Implementation Mapping provided a systematic approach to guide the adaptation process and integrate community voice with the ultimate goal of enhancing sexual health equity among AI/AN youth.