This study explored the elemental, isotopic, and chemometric profiles of Montepulciano d’Abruzzo grapes to ensure the safety and quality of wines produced under the Protected Designation of Origin (PDO) label. Essential nutrients, such as K, P, Ca, Mg, and Fe, were quantified alongside toxic elements, like Hg, Pb, Cd, and As, to evaluate the potential health impacts and compliance with food safety standards. Isotopic analysis provided a powerful tool for geographical authentication, essential for verifying the grapes’ PDO status and preventing market fraud. Chemometric techniques, including Principal Component Analysis (PCA) and Multivariate Classification Methods, were employed to interpret complex datasets, enabling the identification of unique patterns and clusters that signify quality attributes and possible contamination. The study’s findings not only enhance the traceability and authentication processes essential for PDO labels but also offer valuable insights into the safety and quality management of Montepulciano d’Abruzzo grapes, addressing the implications for growers, regulators, and consumers, thereby supporting sustainable viticulture and robust quality control in global wine production.