The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, exploring potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein–protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and, ultimately, atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions.