Monoamine oxidase A (MAO-A) is a major enzyme responsible for the deamination of neurotransmitters such as serotonin (5-HT) in the central nervous system. The decrease in 5-HT levels is accompanied by disorders at the affective and somatic levels, leading to depression and disorders of the satiety center. The aim of this study was to evaluate the degree of MAO-A inhibition by chlorogenic acids, as well as green, light-, and dark-roasted coffee extracts and bioactive compounds from beans of the species Coffea canephora and Coffea arabica. Data for analysis was obtained using isothermal titration calorimetry and molecular docking. The results showed that caffeine and ferulic acid, as well as green Robusta coffee, demonstrated the greatest inhibition of MAO-A activity, which may increase the bioavailability of serotonin. We believe that green coffee shows potential antidepressant activity by inhibiting MAO-A, and may be used for treating depression and potentially, type 2 diabetes.