Therapeutic Potential and Mechanistic Insights of Luteolin in Diabetes Mellitus and Its Associated Disorders

Abstract: The increasing prevalence of diabetes mellitus and its complications remains a major therapeutic challenge. Adverse effects, drug resistance, and inadequate long-term efficacy often limit current pharmacological options. Flavonoids, especially luteolin (LUT), have gained attention as safer, multitargeted agents with the potential to modulate key pathways involved in diabetes and its complications. This review critically evaluates the mechanistic actions, therapeutic potential, and translational relevance of LUT in diabetes, with emphasis on innovative findings in metabolic regulation, oxidative stress, and gut microbiota modulation. A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar (2015–2025) using keywords including “luteolin,” “flavonoid,” “antidiabetic,” “oxidative stress,” “inflammation,” and “diabetic complications.” Peer-reviewed English-language articles reporting in vitro, in vivo, or clinical studies on LUT in diabetes and related disorders were included, while non-peer reviewed sources, unrelated studies, articles without mechanistic data, unavailable full texts, and duplicates were excluded. LUT enhances insulin secretion and sensitivity, improves glucose uptake, and modulates metabolic pathways. Its antioxidant, anti-inflammatory, and anti-glycation effects help mitigate complications such as neuropathy, nephropathy, and retinopathy. Emerging evidence also indicates a role in gut microbiota modulation, suggesting benefits beyond glycemic control. LUT is a promising phytotherapeutic candidate for the management of type 2 diabetes; however, its clinical application is limited by poor bioavailability and scarce human studies. Future research should focus on pharmacokinetic improvements and well-designed clinical trials to confirm efficacy and safety, facilitating its integration into modern antidiabetic strategies.