The polyphenolic structural motif of dietary polyphenols allows them to serve as excellent hydrogen bond donors which in turn help them to strongly interact with various biomacromolecules such as proteins. This interaction is a critical step in the regulatory role of polyphenols on various key proteins involved in cellular physiology. The majority, if not all, of the beneficial effect of polyphenols, can be explained via the functional consequence of proteins it interacts with. Molecular target studies help us to predict therapeutic protein targets for a given small molecule. Herein, we analyzed the predicted interacting proteins/enzymes for EGCG, TF2a, TF2b, TF3, and remdesivir. This study is particularly important in the current context as we think that these polyphenols could target RdRp, an important enzyme that catalyzes the RNA replication in the SARS-CoV-2. Notably, the molecular target analysis suggests that all four polyphenols possess excellent properties of druggability, and they interact with a diverse class of proteins/enzymes. The top 25 target classes of EGCG, TF2a, TF2b, TF3, and remdesivir are represented in the pie-chart, as shown in Figure 8. The detailed output table with the target, common name, UniProt ID, ChEMBL ID, target class, probability, and known actives in 2D/3D are listed in Tables S7–S11 in the Supplementary Information.