The interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) of spike protein with angiotensin-converting enzyme 2 (ACE2) mediates cell invasion. While this interaction mechanism is conserved, the RBD is affected by amino acid mutations in variants such as Delta and Omicron, resulting in enhanced transmissibility and altered ligand binding. Tanshinones are currently investigated as multi-target antiviral agents, but the studies were limited to the original SARS-CoV-2. This study aims at investigating the interaction of tanshinones with the Delta RBD. Chloroquine, methylene blue and pyronaridine, antimalarials previously identified as SARS-CoV-2 RBD binders, were studied for reference. Docking indicated the best scores for tanshinones, while bio-layer interferometry and molecular dynamics highlighted methylene blue as the best Delta RBD binder, although with decreased affinity with respect to the original strain.