<b>Background and Objective:</b> Fucoidan extract from the <i>Sargassum plagiophyllum </i>brown seaweed are renowned for its anticancer and antibacterial activities. Fucoidan is one of the ingredients of <i>S. plagiophyllum </i>that can be extracted by conventional methods and new methods, one of which is microwave assisted extraction (MAE). Research on the extraction of fucoidan from <i>S. plagiophyllum </i>was still limited. Thus, an advanced experiment on how microwave assisted extraction (MAE) of fucoidan was conducted in this study and its activities against <i>Escherichia coli </i>bacteria and HeLa cancer cells were studied. <b>Materials and Methods:</b> <i>Sargassum plagiophyllum </i>was collected from the Gunung Kidul Coast in Yogyakarta, Indonesia. Fucoidan extract of <i>S. plagiophyllum</i> was acquired by applying the MAE method at 600 W for 5 min and using hydrochloric acid as a solvent. The cytotoxicity and antibacterial assays were performed using the MTT assay and the agar plate diffusion methods, respectively. <b>Results:</b> The yield of the fucoidan extract examined was 9.90% (w/w), which consisted of 2.60% sulfate and 2.33 mg 100 g<sup>1</sup> fucose. The finding indicated that fucoidan extract exhibits no antibacterial action and the cytotoxicity against the HeLa cell line was 27.82 mg mL<sup>1</sup>. <b>Conclusion:</b> The MAE technique was proven to support the fucoidan extraction from <i>S. plagiophyllum </i>successfully. Therefore, the fucoidan extract has proven to have promise beneficial in anticancer activity.