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The WHO Package of Essential Non-communicable Diseases Interventions (WHO PEN) provides a core set of measures to prevent, detect and manage non-communicable diseases (NCDs) in low-resource settings. Many countries have adopted WHO PEN to strengthen primary healthcare, yet there is limited consolidated evidence on what components have been implemented and how WHO PEN has been implemented across different contexts. Understanding both the 'what' (disease modules, intervention activities, tools) and the 'how' (strategies, approaches, target populations and contextual factors) is crucial to assess the short-term to medium-term effects on health system readiness, provider performance, patient outcomes and long-term population health impact.This protocol outlines a systematic review that will be updated as new evidence emerges and additional countries adopt or adapt WHO PEN. It represents the first systematic review focused on the implementation of the multifaceted interventions under WHO PEN. Findings will support efforts to sustain and scale up NCD interventions at the primary healthcare level and inform future updates of WHO PEN and related WHO guidance.

We will search PubMed, Web of Science, Cochrane Library and Google Scholar for studies published up to June 2025, supplemented by grey literature and reference checking.The review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Given the complexity, the review will be conducted in two stages. Stage 1 consists of an overview of review, mapping of existing review and evidence and guiding deeper inquiry of stage 2. Stage 2 will conduct a mixed-methods systematic review of the primary studies, forming the main output of this protocol.

Ethics approval is not required. The protocol and findings will be disseminated through peer-reviewed publications, webinars and conferences.

CRD420251064835.