Luteolin, a flavonoid widely distributed in the plant kingdom, contains two benzene rings and hydroxyl groups, and this structural specificity contributes to its diverse biological activities. However, no previous studies have simultaneously investigated the therapeutic potency of luteolin isolated from a plant as an antipsychotic and antidepressant. Here, luteolin exhibited selective inhibition of hMAO-A (IC50 = 8.57 ± 0.47 μM) over hMAO-B (IC50 > 100 μM). In silico proteochemometric modeling predicted promising targets of luteolin, and verification via cell-based G protein-coupled receptor functional assays showed that luteolin is a selective antagonist of the vasopressin receptor V1AR (IC50 = 19.49 ± 6.32 μM) and the dopamine D4 receptor (IC50 = 39.59 ± 1.46 μM). Molecular docking showed the tight binding of luteolin with a low binding score and the high stability of the luteolin-receptor complex, corroborating its functional effect. Thus, hMAO-A, hD4R, and hV1AR are prime targets of luteolin and potential alternatives for the management of neurodegenerative diseases.