BackgroundThe war in Tigray, North Ethiopia which started in November 2020, has destroyed decades of the region’s healthcare success. There is some emerging published evidence on attacks on health care in the region, and we synthesized the available evidence on ‘perilous medicine’ in Tigray to understand the data source, subjects and content covered, and what gaps exist.MethodsWe employed a systematic review and performed a systematic search of MEDLINE, PubMed, CINHAL, Web of Science and Scopus. We included English written documents published from 4 November 2020 to 18–19 October 2022 and updated the search on 23 January 2023. HG and NF independently performed title, abstract and full-text screening. We used Joanna Briggs Institute (JBI) tools to appraise and extract data, and applied content synthesis to analyze. The PROSPERO registration number is CRD42022364964.ResultsOur systematic review search yielded 8,039 documents, and we finally found 41 documents on conflict and health in Tigray. The areas were: (1) attacks on infrastructure, health or aid workers, patients, ambulances or aid trucks identified in 29 documents—the documents reported targeted attacks on health infrastructure and personnel; (2) interruption of health or social services in 31 documents—the documents reported medical and humanitarian siege; (3) outcomes and direct or indirect impacts in 33 documents—the documents reported increased magnitude of illnesses, and catastrophic humanitarian crises including the use of food, medicine and rape as tools of war; and (4) responses, rebuilding strategies, and recommendations in 21 documents—the documents reported improvisation of services, and calling to seize fire, accountability and allow humanitarian.ConclusionsDespite promising studies on conflict and health in Tigray, the documents lack quality of designs and data sources, and depth and diversity of subjects and contents covered; calling further primary studies on a prioritized future research agenda.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13031-023-00524-x.