Antiviral properties of sulfated polysaccharides are related to high molecular mass and sulfate content, while low mass sulfated polysaccharides and oligosaccharides are normally inactive. However, according with literature, sulfated oligosaccharides substituted with hydrophobic groups can be active molecules. Here we describe the semi-synthetic routes for the production of a number of alkyl long-chain ether glycosides of sulfated oligosaccharides and their antiviral activities. For this purpose, red seaweed galactan-derivative oligosaccharides and some of their trityl ethers were submitted to steps of regioselective sulfation and long-chain alkylation through formation of dibutylstannylene acetal intermediates. The semi-synthetic glycosides were tested against three strains of HSV (herpes simplex virus): HSV-1 (F), HSV-2 (G) and HSV-2 (MS). In these assays the IC50 was determined by comparison of non-treated and treated infected-cell cultures. In the determination of the structure-activity relationship, it was observed that the simultaneous presence of a hydrophobic portion and sulfate group is the fundamental requirement for the activity of these compounds. The activity appears to increase with an appropriated balance between the sulfate groups and the hydrophobic portions. In addition, the monoalkylated glycoside containing one sulfate group located at C-4 of the galactopyranosidic ring was the most active compound.