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While levodopa (L\u2010DOPA) remains the gold standard for symptomatic treatment, its long\u2010term administration is associated with complications such as motor fluctuations, dyskinesia, and oxidative stress. Given these limitations, interest has grown in plant\u2010derived bioactive compounds for their potential neuroprotective and disease\u2010modifying effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic literature review was conducted across PubMed, Scopus, Google Scholar, and Web of Science, focusing on peer\u2010reviewed studies published between 2023 and March 2025. The inclusion criteria targeted in\u00a0vitro and in\u00a0vivo preclinical studies as well as clinical trials that directly compared levodopa with plant\u2010derived compounds in the context of PD. Key search terms included \u201cParkinson's disease,\u201d \u201clevodopa,\u201d \u201cphytochemicals,\u201d and \u201cplant\u2010based neuroprotection\u201d.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Recent studies have highlighted several classes of plant\u2010based compounds\u2014including polyphenols (resveratrol, curcumin, EGCG), flavonoids (quercetin, apigenin, naringenin), alkaloids (berberine, caffeine, L\u2010DOPA derived from <jats:italic>Mucuna pruriens<\/jats:italic>), and terpenoids (ginkgolide B, celastrol)\u2014as potential neuroprotective agents. These compounds exert multiple actions, such as reducing oxidative stress, blocking neuroinflammation, preventing \u03b1\u2010synuclein aggregation, and protecting mitochondria. Although levodopa effectively addresses motor symptoms, these phytochemicals may complement conventional therapy by targeting underlying disease processes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although levodopa is indispensable for the symptomatic management of PD, emerging evidence supports the integration of plant\u2010derived bioactive compounds as adjunct therapies with disease\u2010modifying potential. Future research should prioritize improving bioavailability, developing standardized formulations, and conducting long\u2010term clinical trials to evaluate the translational applicability of these natural agents in Parkinson's disease therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70540","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T06:26:11Z","timestamp":1755152771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Levodopa and Plant\u2010Derived Bioactive Compounds in Parkinson's Disease: Mechanisms, Efficacy, and Future Perspectives"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-3402","authenticated-orcid":false,"given":"Emre","family":"Akta\u015f","sequence":"first","affiliation":[{"name":"Faculty of Art and Science, Molecular Biology and Genetics Y\u0131ld\u0131z Technical University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4624-4428","authenticated-orcid":false,"given":"Ha\u015fmet Ayhan","family":"Hana\u011fas\u0131","sequence":"additional","affiliation":[{"name":"Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-6303","authenticated-orcid":false,"given":"Nehir \u00d6zdemir","family":"\u00d6zgent\u00fcrk","sequence":"additional","affiliation":[{"name":"Faculty of Art and Science, Molecular Biology and Genetics Y\u0131ld\u0131z Technical University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14426"},{"key":"e_1_2_17_3_1","unstructured":"M.Aijaz A.Kumar M.Ahmad andM. 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