Stilbene dimers are well-known for their diverse biological activities. In particular, previous studies have demonstrated the high antibacterial potential of a series of trans-δ-viniferin-related compounds against gram-positive bacteria such as Staphylococcus aureus. The trans-δ-viniferin scaffold has multiple chemical functions and can therefore be modified in various ways to generate derivatives. Here we report the synthesis of 40 derivatives obtained by light isomerization, O-methylation, halogenation and dimerization of other stilbene monomers. The antibacterial activities of all generated trans-δ-viniferin derivatives were evaluated against S. aureus and information on their structure–activity relationships (SAR) was obtained using a linear regression model. Our results show how several parameters, such as the O-methylation pattern and the presence of halogen atoms at specific positions, can determine the antibacterial activity. Taken together, these results can serve as a starting point for further SAR investigations.