Wild species of the subgenus Amygdalus (genus Prunus and family Rosaceae) have been insufficiently studied with regard to their chemical components and their pharmacological potential. The present study aimed at the investigation of the chemical composition of leaves and twigs of A. orientalis Mill. and A. zielinskii Browicz, thus assessing the antioxidant and enzyme inhibiting potential, as well as to define the safety profile. Our results showed that extracts were rich in phenolics, and liquid chromatography-diode array detector-tandem mass spectrometry (LC-DAD-MS) analysis allowed the identification of phenolic acids, flavonoids, coumarins, proanthocyanins, amino acids, fatty acids and derivatives. The assessment of the antioxidant potential demonstrated that the ethyl acetate extract of A. zielinskii twigs recorded the highest anti-ABTS (2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (1298.10 mg trolox equivalent (TE)/g), total antioxidant (4.98 mmol TE/g), Cu++(1211.47 mg TE/g) and Fe+++ (907.86 mg TE/g) reducing properties. In addition, it also had the highest anti-DPPH (2,2-diphenyl-1-picrylhydrazyl) activity (560.17 mg TE/g), together with its methanolic extract and that of A. orientalis twigs, whereas the best chelation power was exerted by the ethyl acetate extract of A. orientalis leaves (31.10 mg EDTAE/g). Regarding enzyme inhibition, methanolic extracts of the leaves and twigs of both species displayed the highest α-glucosidase and tyrosinase inhibitory activity, while ethyl acetate extracts of A. orientalis twigs and leaves revealed the best butyrylcholinesterase (2.35 mg galantamine equivalent (GALAE)/g) inhibitory activity. Docking studies demonstrated strong binding affinities of compounds like rutin, kaempferol derivatives, and isorhamnetin-3-O-rutinoside with the abovementioned enzymes, supporting the consistent inhibitory potential. Moreover, we investigated the potential cytotoxicity of these extracts in different human cell lines, thus proving their safety. These results highlight the potential of the two Amygdalus species as a new source of bioactive molecules for the development of health-promoting applications.