Seeds of L. with a high content of bioactive compounds are valuable by-products from grape processing. However, little is known about the bioactivity of seeds from other species. The aim of this study has been to compare the phenolic composition, antimicrobial activity, and antioxidant activity of extracts from seeds of four species ( Michx., Benth., Rupr., and L.). Antioxidant activities were assessed as ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, and oxygen radical absorbance capacity (ORAC). The antimicrobial activity was determined using the microdilution method against some Gram-negative (, ser. Typhimurium, and ) and Gram-positive ( and ) bacteria. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to evaluate the phenolic profile of extracts. Flavan-3-ols, procyanidins, phenolic acids, flavonols, anthocyanins, and stilbenoids were detected. (+)-Catechin and (-)-epicatechin turned out to be the most abundant in the phenolic profile of seed extract. Phenolic acids prevailed in the extract from seeds. The and seed extracts had higher contents of most individual phenolics compared to the other species. They also showed a higher total phenolic content, DPPH scavenging activity, ORAC, and overall antibacterial activity. Total phenolic content significantly correlated with antioxidant activity and antimicrobial activity against . The principal component analysis (PCA) showed discrimination between , , and clustered and with respect to variables. To recapitulate, this research demonstrates that seeds of different species, especially and , are sources of molecules with antioxidant and antimicrobial activities that can be used in different sectors, such as in the food, cosmetic, and pharmaceutical industries.