This study investigated the in vitro simulated gastrointestinal digestion (GID) effects on wild and micropropagated Apennines Genepì infusions. Wild and micropropagated infusions were compared for their antioxidant activity, phenolic contents, and polyphenolic profiles before and after GID. Before digestion, the wild infusions had higher amounts of phenolic compounds and antioxidant activity than the micropropagated ones. Instead, after digestion, the differences in the total phenolic content (TPC) and antioxidant activity between wild and micropropagated infusions were less pronounced. The changes in the TPC and phenolic profiles revealed the presence of several chemical transformations and rearrangements that resulted in compounds with different reactivity and antioxidant potential. Without enzyme actions, the wild infusion digest undergoes higher modifications than those obtained from the micropropagated ones. The current study offers the first concrete proof of the impact of GID on the polyphenolic chemicals present in infusions of wild and micropropagated Apennines Genepì and their antioxidant properties. Our findings are essential for future in-depth analyses of Apennine Genepì infusions and their potential impacts on human health.