Background: Glutathione and glutathione metabolism enzymes are essential for the normal functioning of cells and tissues and maintenance of body homeostasis. The aim of our study was to investigate the influence of the new Schiff bases, and their combinations with 3d metals, on the glutathione metabolism in the liver in physiological conditions. Material and methods: An experimental study of laboratory animals (rats) was performed. New local biologically active compounds (BAC) – CMD-4, CMD-8 and CMJ-23, were injected to healthy rats for 14 days. The content of glutathione (total, reduced and oxidized) and the activity of glutathione reductase (GR), glutathione peroxidase (GPO), glutathione-S-transferase (GST) and glutaredoxin (GRX) were determined in the liver homogenates. results: All tested BAC statistically significant decreased the level of reduced and total glutathione (about 20-30%), and GMJ-23 also reduced the oxidized glutathione in the liver (-48%, p<0.05). Influence on the activity of enzymes of glutathione metabolism was more ambiguous. Administration of CMD-4, CMD-8 and CMJ-23 did not produce conclusive changes of the enzyme activity of the glutathione metabolism, and their induction had only tendency of GR, GST and GRX activity decrease, while CMT-28 and CMT-67 preferentially modulated the activity of enzymes. conclusions: Local BAC exerts an individual influence on the glutathione metabolism in physiological conditions, which may be used for a particular regulation of the processes according to the cell needs.