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Luteolin is widely distributed phytochemical, a flavonoid, in kingdom plantae. Luteolin with potential antioxidant activity prevent ROS-induced damages and reduce oxidative stress which is mainly responsible in pathogenesis of many diseases. Several chemo preventive activities and therapeutic benefits are associated with luteolin. Luteolin prevents cancer via modulation of numerous pathways, that is, by inactivating proteins; such as procaspase-9, CDC2 and cyclin B or upregulation of caspase-9 and caspase-3, cytochrome C, cyclin A, CDK2, and APAF-1, in turn inducing cell cycle arrest as well as apoptosis. It also enhances phosphorylation of p53 and expression level of p53-targeted downstream gene. By Increasing BAX protein expression; decreasing VEGF and Bcl-2 expression it can initiate cell cycle arrest and apoptosis. Luteolin can stimulate mitochondrial-modulated functions to cause cellular death. It can also reduce expression levels of p-Akt, p-EGFR, p-Erk1/2, and p-STAT3. Luteolin plays positive role against cardiovascular disorders by improving cardiac function, decreasing the release of inflammatory cytokines and cardiac enzymes, prevention of cardiac fibrosis and hypertrophy; enhances level of CTGF, TGFβ1, ANP, Nox2, Nox4 gene expressions. Meanwhile suppresses TGFβ1 expression and phosphorylation of JNK. Luteolin helps fight diabetes via inhibition of alpha-glucosidase and ChE activity. It can reduce activity levels of catalase, superoxide dismutase, and GS4. It can improve blood glucose, insulin, HOMA-IR, and HbA1c levels. This review is an attempt to elaborate molecular targets of luteolin and its role in modulating irregularities in cellular pathways to overcome severe outcomes during diseases including cancer, cardiovascular disorders, diabetes, obesity, inflammation, Alzheimer's disease, Parkinson's disease, hepatic disorders, renal disorders, brain injury, and asthma. As luteolin has enormous therapeutic benefits, it could be a potential candidate in future drug development strategies., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)