Background/Objectives: Silver nanoparticles (AgNPs) hold great promise for antimicrobial, antiviral, and anticancer applications; however, concerns about their toxicity remain a major barrier to their medical use. This study systematically evaluates the acute oral toxicity of five well-characterized AgNP formulations from the Argovit™ family, which previously showed remarkable biomedical properties. Methods: We determine the median lethal dose (LD50), assess clinical signs, and identify the histopathological alterations in mice following oral administration for each formulation. The LD50 was calculated for AgNPs (metallic silver plus stabilizing agent) and for the complete formulation (including water). Results: All formulations showed exceptionally high LD50 values (86,020–150,535 mg/kg) considering the complete formulation, surpassing those reported for other AgNPs in the literature (typically ≤5,000 mg/kg). Clinical signs and toxicological assessment reveal differences in the response of the AgNPs formulations, but all exhibit extremely low toxicity. Histopathological changes were minimal compared to those caused by other AgNP formulations, even though we used doses several times higher. The estimated human LD50 values for the assessed Argovit AgNPs formulations are 17-30 times higher than those reported for other AgNP formulations in the literature. Conclusions: The remarkably low toxicity found in this work contradicts the prevailing assumption that only biogenically synthesized AgNP are biocompatible, highlighting these synthetic PVP-AgNP formulations as a highly safe alternative. The study suggests that the low LD50 may be due to the peculiar structure of Argovit AgNP formulations, which, according to recent data, consists of Ag cores incorporated into PVP nano- and microgels. A high percentage of rapid elimination of Argovit AgNPs from organisms (>98%) via feces also contributes to low LD50. To our knowledge, the present work is the first to study the LD50 of AgNPs-nanogel systems.