Postbiotics are increasingly incorporated into functional foods and supplements due to their potential health benefits, particularly immune modulation. However, the mechanisms by which these products influence antiviral immunity remain incompletely understood. Type I interferons, especially interferon-α (IFN-α), are central mediators of early antiviral defense, acting primarily through the activation of plasmacytoid dendritic cells (pDCs). Five commercially available postbiotic products containing heat-killed bacterial strains were evaluated for their ability to stimulate pDCs and induce IFN-α production. Bacterial uptake by pDCs was analyzed using confocal microscopy with Z-stack imaging, and IFN-α levels were quantified by ELISA. Among the tested strains, only Lactococcus lactis strain Plasma (LC-Plasma) demonstrated significant internalization by pDCs and induced measurable IFN-α production (73.8 ± 2.5 pg/mL) at the recommended daily dose. This effect was not observed with other strains, even at higher bacterial loads (up to 1 × 10¹¹ cells). Z-stack imaging confirmed that LC-Plasma was actively phagocytosed by pDCs, whereas other strains, such as L. paracasei MCC1849, adhered to the cell surface without internalization. The pDC concentration used in the assay approximated physiological levels in human blood. Notably, the IFN-α level induced by LC-Plasma exceeded that reported in the serum of hospitalized COVID-19 patients. L. lactis strain Plasma uniquely activates pDCs and induces IFN-α production under physiologically relevant conditions, distinguishing it from other postbiotic strains. These findings suggest that LC-Plasma may serve as a functional postbiotic with the potential to enhance antiviral immunity and mitigate disease severity.