Background. GSH metabolism dysorders are widely recognized as central pathogenetic link feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. Identification, research and testing of new remedies for correction of the glutathione system disorders in asthma are of particular interest due to the increased incidence and severity of this pathological process, which leads to the disability of working age people. In this regard, local bioactive compounds (BC)  Schiff base, their combination with 3d metals that exhibit strong antioxidant, antiproliferative and cytotoxic effects are of special interest [Gulea A. et al., 2009, 2013]. However, their influence on the level of GSH and glutathione metabolism enzyme’s activity in physiological conditions and patients with asthma had not been studied. The aim of this research was to study in vitro the peculiarities of the local BC action on glutathione system in physiological conditions and in persistent asthma. Methods. The research was done on peripheral blood samples collected from 42 patients with mild, moderate and severe forms of persistent asthma, who have been treated at the Pneumology Department of the "Chiril Draganiuc" Institute of Phtiziopneumology. Local BC  CMD-4, CMD-8, CMJ-23 and CMJ-33, were synthesized at the Inorganic Chemistry Department of Moldova State University [Gulea A., 2009]. The blood was collected in the morning after fasting from the cubital vein and then, under sterile conditions, was placed in a vial containing 8 ml of Dulbecco's modified Eagle medium (DMEM), heparin (2.5 un/ml) gentamicin (100 mg/ml) and L-glutamine (0.6 mg/ml). For the study of the influence on glutathione system of the local BC 1.0 ml of this mixture was pipetted into 6 sterile tubes. 0.1 ml 0.9% NaCl were added into the first tube for the assay of the initial level of the studied indices. The tested BC, diluted in 0.1 ml 0.9% NaCl to a final concentration 50 nM/ml, were added into rest test-tubes. After 24 hours incubation at 37°C, the tubes were centrifuged for 5 minutes at 1500 rev/min. The glutation reductase (GR), thioredoxin reductase (TR) glutation peroxidase (GPO) and glutathione-S-transferase (GST) activity were evaluated in supernatants by spectrophotometric micromethod adapted to the Hybrid Multi-mode Microplate Rider Synergy H1, "BioTek" (USA). Results. It was established that in healthy people the compounds CMD-4, CMD-8, CMJ-33 and CMJ-23 does not change the GR and GST activity; the CMD-4 decreases, and the CMD-8 and CMJ-23 increase the activity of TR. The activity of GPO decrease after CMD-4, CMD-8 and CMJ-33 administration compared to baseline. In the mild form of asthma all studied BC exercise potent modulatory effects on glutathione metabolic enzymes, as confirmed by the increase of the TR, GST and GPO activity compared with healthy individuals. In moderate forms of asthma the studied BC increase the GR, TR, GST, and GPO values, and in the severe forms of asthma the BC mainly reduce the GR, TR and GST activity. Conclusions: The study established the effectiveness of local bioactive compounds  CMD-4, CMD-8, CMJ-33 and CMJ -23, confirmed by their ability to improve the functional state of glutathione system in different forms of persistent asthma and to maintain the thiol-disulfide cell balance, which would allow the development of new treatment strategies of asthma.