AbstractFive Australian seaweed species, Phyllosphora comosa, Ecklonia radiata, Durvillaea potatorum, Sargassum fallax, and Cystophora siliquosa, thrive along the country's shorelines. Some of these seaweeds have recognized health benefits but have not been fully investigated in terms of their bioactive components and mechanisms of action. We employed ultrasonication with 70% methanol to extract phenolic compounds from these seaweeds and investigated a range of bioactivities for these extracts, including anti‐inflammatory activity exploring urease inhibition, nitric oxide scavenging activity, protein denaturation inhibition, and protease inhibition. Anti‐diabetic activities were investigated using α‐amylase and α‐glucosidase inhibition assays. Anti‐proliferative and anti‐mitotic activities were evaluated using yeast‐cell and green‐gram models, respectively. Our findings showed that C. siliquosa inhibited nitric oxide, urease, and protease activities, with S. fallax, P. comosa, and E. radiata exhibiting substantial inhibition of protein denaturation. E. radiata displayed inhibitory effects on both α‐amylase and α‐glucosidase, whereas P. comosa targeted only the α‐glucosidase enzyme, indicating different mechanisms of anti‐diabetic activity. In these anti‐mitotic assays, C. siliquosa exhibited low cell viability and a significant anti‐proliferative effect, particularly within 24 h, while E. radiata demonstrated notable inhibition at 48 h. LC‐ESI‐QTOF‐MS/MS investigation identified 48 phenolic compounds, including 19 phenolic acids, 20 flavonoids, and 9 other polyphenols. The presence of these compounds in extracts correlated with observed biological activities. These results support the potential health benefits of these seaweeds and link this activity to the presence of bioactive phenolics.