Glioblastoma remains the most common and aggressive primary tumor of the central nervous system in adults. Current treatment options include standard surgical resection combined with radiation/chemotherapy, but such protocol most likely only delays the inevitable. Therefore, the problem of finding therapeutic targets to prevent the occurrence and development of this severe oncological disease is currently acute. It is known that the functions of selenoproteins in the regulation of carcinogenesis processes are not unambiguous. Either they exhibit cytotoxic activity on cancer cells, or cytoprotective. A special place in the progression of oncological diseases of various etiologies is occupied by proteins of the thioredoxin and glutathione systems. These are two cellular antioxidant systems that regulate redox homeostasis, counteracting the increased production of reactive oxygen species in cells. The review reflects the latest data on the role of key enzymes of these redox systems in the regulation of processes associated with the progression of glioblastoma. A thorough consideration of these issues will expand fundamental knowledge about the functions of selenium-containing thioredoxin reductases and glutathione peroxidases in the therapy of glioblastomas and provide an understanding of the prospects for the treatment of this aggressive oncological disease.