In this study, Sophora flavescens (SF) from Yeongcheon (YSF) and Mt. Jiri (JiSF), and Angelica gias (AG) from Yeongcheon (YAG), Mt. Jiri (JiAG), and Jecheon (JeAG) were extracted using three concentrations of ethanol, 95% (95Et), 70% (70Et), and 50% (50Et), and hot water (DW) to evaluate the inhibitions of monoamine oxidases (MAOs; MAO-A and B), cholinesterases (ChEs; AChE and BChE) and β-secretase (BACE1) for targeting depression and neurodegenerative diseases. There were no significant differences in constituent compounds depending on herbal origins, except that YSF-95Et and JiSF-95Et showed a distinct non-polar spot upper maackiain position, and JiAG and JeAG showed a higher amount of decursin than YAG. Ethanolic YAG and JeAG extracts showed the highest MAO-A inhibition, and YSF-95Et mostly inhibited MAO-B. JiSF-95Et showed the highest AChE inhibition and YSF-70Et, JiSF-95Et, and -70Et showed the highest BChE inhibition. Interestingly, ethanolic AG extracts showed extremely potent BACE1 inhibition, especially for JiAG-95Et and JeAG-50Et, whereas there have been no reports about BACE1 inhibition of decursin, the major compound, or AG extracts in other studies. All extracts were nontoxic to MDCK and SH-SY5Y with a low toxicity to HL-60. The results showed a different pattern of inhibitory activities of the extracts toward target enzymes depending on the origins, and multi-target abilities, especially for MAO-B and BChE by YSF-95Et, for AChE and BChE by JiSF-95Et, and for MAO-B and BACE1 by JiAG-95Et. It is suggested that those extracts are potential candidates for finding novel compounds with multi-target inhibitory activities, and herbal origin is an important factor to be considered in selection of the plants.