Phoradendron brachystachyum is an American mistletoe distributed in México and used ethnobotanically in infusions to treat hypertriglyceridemia and lower cholesterol levels. This study aimed to evaluate the bioaccessibility of the phenolic acids from mistletoe infusions and the effect of simulated digestion on its antioxidant and lipase inhibitory properties. The in vitro digestion process decreased the antioxidant capacity activity by the TEAC and ORAC assays in infusions from leaves, stems, and whole plant samples. Moreover, the individual phenolic content of mistletoe infusions was also affected by the in vitro digestion process; the most abundant individual phenolic constituents at the end of the digestion process were ferulic and quinic acids. These compounds showed low bioaccessibility values ranging from 7.48% to 22.60%. In addition, the in vitro digestion diminished the pancreatic lipase inhibition percentage of leaves and whole plant infusions but increased it in the stem samples. This research showed that given the phenolic content and pancreatic lipase inhibitory activity of mistletoe infusions, it could be used as a potential source for the development of functional foods and nutraceuticals; nonetheless, its phenolic content is affected by gastrointestinal digestion; thus, encapsulation strategies are encouraged to protect these metabolites from the gastrointestinal environment while preserving their antioxidant and hypolipidemic potentials.