Amphiphilic polymers are promising candidates for novel fouling-release coatings for marine applications. We grafted amphiphilic alginates with fluorinated side chains to glass and silicon substrates and characterized the obtained films by contact angle goniometry, spectroscopic ellipsometry, XPS, and ATR-FTIR. The potential to inhibit protein attachment was tested against four different proteins, and intermediate fluorine loadings showed the strongest reduction with respect to hydrophobic, aliphatic controls. A similar trend was observed in dynamic attachment experiments using Navicula perminuta diatoms and settlement experiments with zoospores of the green algae Ulva linza. The results indicate that amphiphilic alginates are promising natural and renewable biomacromolecules that could be included in future protective coating technologies.