Plant diversity around the world, as well as the chemical variation, involves a large amount of bioactive substances. The use of plant extracts with biological properties appears as a viable and healthy alternative when compared to synthetic substances. In this context, the objective of this study was to evaluate the aqueous extracts of native and cultivated leaves of Physalis angulata L., as well as the influence of the extraction method on the bioaccessibility of bioactive compounds, antioxidant activity and antimicrobial activity. The extracts were obtained from the native and cultivated leaves of P. angulata using three different extraction methods: decoction, maceration and an ultrasound-assisted method. The analysis of variance showed significant differences between the extraction methods and the type of plant material. The extracts obtained by decoction showed the highest levels of phenolic compounds and higher antioxidant potential for both analytical methods (ABTS and DPPH), differing significantly from the other extraction methods. The bioaccessibility indices of the phenolic compounds obtained from the extracts were considered reduced after the simulated gastrointestinal digestion, and consequently, showed low antioxidant potential. The antimicrobial potential of the extracts was observed against the Gram-positive bacteria Staphylococcus aureus and Listeria monocytogenes.