In recent years, short plant peptides have emerged as highly promising, innovative bioregulators of crop growth and resilience. Activating systemic defense using synthetic plant peptides represents a potent strategy to improve crop resistance against pathogenic threats. Potato virus Y (PVY) causes devastating economic losses in potato () crops. In this study, we investigated the protective activity of synthetic analogs of systemin, a classic defense peptide originally discovered within the Solanaceae family. We synthesized the putative potato octadecapeptide systemin (AVHSTPPSKRDPPKMQTD) along with two 17-mer variants, each truncated by a single amino acid residue at either the N- or C-terminus, for foliar application. The defensive efficacy of these peptides was evaluated using inoculation and monitoring viral accumulation under controlled growth chamber conditions. Foliar application of all three synthetic peptides significantly reduced the accumulation of the PVY ordinary strain over a one-month post-infection period with comparable efficacy. Furthermore, we demonstrated the antiviral effect of the synthetic octadecapeptide against the exceptionally devastating and widespread recombinant PVY strain. These findings suggest that synthetic derivatives of potato systemin could serve as potential tools for developing eco-friendly antiviral strategies for sustainable crop protection.