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Inflammation is a vital protective response to threats, but it can turn harmful if chronic and uncontrolled. Key elements involve pro-inflammatory cells and signaling pathways, including the secretion of pro-inflammatory cytokines, NF-κB, reactive oxygen species (ROS) production, and the activation of the NLRP3 inflammasome. <i>Ampelopsis grossedentata</i>, or vine tea, contains dihydromyricetin (DHM) and myricetin, which are known for their various health benefits, including anti-inflammatory properties. Therefore, the aim of this study is to assess the impact of an extract of <i>A</i>. <i>grossedentata</i> leaves (50 µg/mL) on inflammation factors such as inflammasome, pro-inflammatory pathways, and macrophage polarization, as well as its antioxidant properties, with a view to combating the development of low-grade inflammation. <i>Ampelopsis grossedentata</i> extract (APG) significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFNγ, IL-12, IL-2, and IL-17a) in human leukocytes. In addition, APG reduced LPS/IFNγ -induced M1-like macrophage polarization, resulting in a significant decrease in the expression of the pro-inflammatory cytokines TNF-α and IL-6, along with a decrease in the percentage of M1 macrophages and an increase in M0 macrophages. Simultaneously, a significant decrease in NF-κB p65 phosphorylation and in the expression of inflammasome genes (<i>NLRP3, IL-1β</i> and <i>Caspase 1</i>) was observed. The results suggest that <i>Ampelopsis grossedentata</i> could be a promising option for managing inflammation-related chronic diseases. Further research is needed to optimize dosage and administration methods.