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Current treatments are palliative, primarily focusing on blood glucose modulation. This review systematically evaluates 181 bioactive compounds isolated from 66 marine fungal strains for their inhibitory activities against key diabetes-related enzymes, including \u03b1-glucosidase, protein tyrosine phosphatase 1B (PTP1B), dipeptidyl peptidase-4 (DPP-4), glycogen synthase kinase-3\u03b2 (GSK-3\u03b2), and fatty acid-binding protein 4 (FABP4). These compounds, categorized into polyketides, alkaloids, terpenoids, and lignans, exhibit multitarget engagement and nanomolar-to-micromolar potency. The review highlights the potential of marine fungal metabolites as novel antidiabetic agents, emphasizing their structural novelty and diverse mechanisms of action. Future research should focus on overcoming challenges related to yield and extraction, leveraging advanced technologies such as genetic engineering and synthetic biology to enhance drug development.<\/jats:p>","DOI":"10.3390\/md23040142","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T06:58:43Z","timestamp":1742972323000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Marine Fungal Metabolites as Potential Antidiabetic Agents: A Comprehensive Review of Their Structures and Enzyme Inhibitory Activities"],"prefix":"10.3390","volume":"23","author":[{"given":"Zimin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatric intensive Care Medicine, Hainan Women and Children\u2019s Medical Center, Haikou 570100, China"},{"name":"Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Polysaccharide Materials and Modification, School of of Marine Science and Biotechnology, Guangxi Minzu University, Nanning 530006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meirong","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food and Pharmaceutical Engineering, Guangxi Vocational University of Agriculture, Nanning 530006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Polysaccharide Materials and Modification, School of of Marine Science and Biotechnology, Guangxi Minzu University, Nanning 530006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fandong","family":"Kong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Polysaccharide Materials and Modification, School of of Marine Science and Biotechnology, Guangxi Minzu University, Nanning 530006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxin","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Polysaccharide Materials and Modification, School of of Marine Science and Biotechnology, Guangxi Minzu University, Nanning 530006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric intensive Care Medicine, Hainan Women and Children\u2019s Medical Center, Haikou 570100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2004","DOI":"10.1002\/hsr2.2004","article-title":"Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused","volume":"7","author":"Hossain","year":"2024","journal-title":"Health Sci. 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