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Ethnopharmacological Relevance: Pomegranate 'Punica granatum' offers multiple health benefits, including managing hypertension, dyslipidemia, hyperglycemia, insulin resistance, and enhancing wound healing and infection resistance, thanks to its potent antioxidant and anti-inflammatory properties. It has been symbolized by life, health, femininity, fecundity, and spirituality., Aim of the Study: Although laboratory and animal studies have been conducted on the healing effects of pomegranate, there needs to be a comprehensive review on its anti-oxidative and anti-inflammatory effects in chronic disorders. We aim to provide a comprehensive review of these effects based on in-vitro, in-vivo, and clinical studies conducted in managing various disorders., Materials and Methods: A comprehensive search of in-vitro, in-vivo, and clinical findings of pomegranate and its derivatives focusing on the highly qualified original studies and systematic reviews are carried out in valid international web databases, including Web of Science, PubMed, Scopus, and Cochrane Library., Results: Relevant studies have demonstrated that pomegranate and its derivatives can modulate the expression and activity of several genes, enzymes, and receptors through influencing oxidative stress and inflammation pathways. Different parts of pomegranate; roots, bark, blossoms, fruits, and leaves contain various bioactive compounds, such as polyphenols, flavonoids, anthocyanins, and ellagitannins, that have preventive and therapeutic effects against many disorders such as cardiovascular diseases, diabetes, neurological diseases, and cancers without any serious adverse effects., Conclusions: Most recent scientific evidence indicates that all parts of the pomegranate can be helpful in treating a wide range of chronic disorders due to its anti-oxidative and anti-inflammatory activities. Since the safety of pomegranate fruit, juice, and extracts is established, further investigations can be designed by targeting its active antioxidant and anti-inflammatory constituents to discover new drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)