The aim of present study is to compare and evaluate the biological activities of ethyl acetate (EtOAc), methanolic (MeOH), and aqueous extracts from Amygdalus communis hulls based on enzyme inhibition and antioxidant capacities together with screening of biomolecules. Phenolics were estimated by calculating total phenolic (TPC) and flavonoid (TFC) content as well as individual biocompounds using LC-ESI-MS/MS. The antioxidant power was determined using six different assays. The enzyme inhibitory activities were investigated for the first time against alpha-amylase and tyrosinase. Results showed that the aqueous extract exerted the better antioxidant activities (cupric ion reducing power, ferric ion reducing power, scavenging ability towards DPPH radical, ABTS(+) free radical scavenging and ferrous ion chelating), except for total antioxidant capacity (ethyl acetate extract). Methanol extract showed the highest inhibitory activity toward tyrosinase while ethyl acetate extract was the most effective against alpha-amylase. Catechin (4120-14820 mu g/g extract), epicatechin (330-1470 mu g/g extract), hyperoside (235-420 mu g extract), and hesperidin (138-250 mu g/g extract) were the most abundant compounds. The present work recommends Amygdalus communis hulls, an almond by-product, as a potential source of natural biomolecules beneficial for human health.