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This review will focus on the emerging processes for the generation and isolation of bioactive peptides or cryptides from algae, including: (1) pre-treatments of algae for the extraction of protein by physical and biochemical methods; and (2) methods for the generation of bioactive including enzymatic hydrolysis and other emerging methods. To date, the main biological properties of the peptides identified from algae, including anti-hypertensive, antioxidant and anti-proliferative\/cytotoxic effects (for this review, anti-proliferative\/cytotoxic will be referred to by the term anti-cancer), assayed in vitro and\/or in vivo, will also be summarized emphasizing the structure\u2013function relationship and mechanism of action of these peptides. Moreover, the use of in silico methods, such as quantitative structural activity relationships (QSAR) and molecular docking for the identification of specific peptides of bioactive interest from hydrolysates will be described in detail together with the main challenges and opportunities to exploit algae as a source of bioactive peptides.<\/jats:p>","DOI":"10.3390\/md20050317","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T21:52:11Z","timestamp":1652219531000},"page":"317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Bioactive Peptides from Algae: Traditional and Novel Generation Strategies, Structure-Function Relationships, and Bioinformatics as Predictive Tools for Bioactivity"],"prefix":"10.3390","volume":"20","author":[{"given":"Jack","family":"O\u2019Connor","sequence":"first","affiliation":[{"name":"School of Biological & Health Sciences, Technological University Dublin, Dublin 2, Ireland"},{"name":"Department of Food Chemistry and Technology, Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9939-063X","authenticated-orcid":false,"given":"Marco","family":"Garcia-Vaquero","sequence":"additional","affiliation":[{"name":"Section of Food and Nutrition, School Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Meaney","sequence":"additional","affiliation":[{"name":"School of Biological & Health Sciences, Technological University Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brijesh Kumar","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Technology, Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12571-015-0427-z","article-title":"Feeding 9 billion by 2050\u2014Putting fish back on the menu","volume":"7","author":"Barange","year":"2015","journal-title":"Food Secur."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/gcbb.12579","article-title":"Microalgae for integrated food and fuel production","volume":"11","author":"Weickert","year":"2019","journal-title":"GCB Bioenergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129800","DOI":"10.1016\/j.chemosphere.2021.129800","article-title":"Microalgae as sustainable food and feed sources for animals and humans\u2014Biotechnological and environmental aspects","volume":"271","author":"Kusmayadi","year":"2021","journal-title":"Chemosphere"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.biortech.2012.10.135","article-title":"Biorefinery of microalgae for food and fuel","volume":"135","author":"Wijffels","year":"2013","journal-title":"Bioresour. 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