World Scientific Research

Diabetes mellitus (DM) affects approximately 537 million adults worldwide, and this number is expected to increase to 783 million by 2045, highlighting the urgent need for effective and affordable therapeutic strategies. In Ethiopia, where nearly 80% of the population depends on traditional medicine for primary healthcare, more than 30 medicinal plant species have demonstrated antidiabetic activity in experimental studies. Despite these promising findings, the molecular mechanisms responsible for their hypoglycemic effects remain insufficiently characterized. This review examines the therapeutic potential of Ethiopian antidiabetic medicinal plants through the emerging integration of metabolomics and network pharmacology. A systematic literature review of studies published between 2015 and 2025 was conducted using PubMed, Scopus, Web of Science, and Google Scholar following PRISMA guidelines. Thirty-five medicinal plant species belonging to 24 botanical families were identified, with leaves and hydro-methanolic extracts representing the predominant research focus. Species such as Thymus schimperi, Hagenia abyssinica, Aloe spp., Bersama abyssinica, Verbascum sinaiticum, and Justicia schimperiana exhibited substantial antidiabetic potential. Recent metabolomics and network pharmacology investigations have revealed bioactive metabolites targeting insulin signaling, AMPK activation, inflammation, glucose metabolism, and gut microbiota regulation. Integrating metabolomics, network pharmacology, molecular docking, and multi-omics validation provides a comprehensive framework for identifying active compounds, elucidating mechanisms of action, and accelerating evidence-based phytomedicine development. Standardized phytochemical profiling, computational target prediction, and adherence to biodiversity and ethical guidelines are essential for translating Ethiopian medicinal plants into clinically relevant antidiabetic therapeutics.