<p>The review is focused on the analysis of published data on the normalizing and protective activity of the neuroprotective peptide of HLDF-6 family. The peptide HLDF-6 (TGENHR) corresponds to fragment 41–46 of the protein differentiation factor HLDF (Human Leukemia Differentiation Factor). The neuroprotective, nootropic, anxiolytic, differentiating, antitumor, and anti-aging effects of the peptides HLDF-6 and its analogue HLDF-6-H (TGEXHR, where X is Hse) are mediated by their interaction with key targets, including the NMDA and metabotropic glutamate, serotonin, and opioid systems. In cellular and experimental models of Alzheimer’s disease induced by the administration of beta-amyloid peptide Aβ25–35, as well as a transgenic model of Alzheimer’s disease using B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) mice, the HLDF-6 peptide exhibits neuroprotective and nootropic activity. Chronic use of HLDF-6 peptide at a dose of 250 μg/kg is accompanied by a neuroprotective effect, normalizes steroidogenesis and effectively stimulates the performance of cognitive tasks. In an experimental model of Parkinson’s disease (PD), HLDF-6-H peptide exhibits neuroprotective, anxiolytic and antidepressant activity. Chronic use of HLDF-6-H peptide (intranasally, 3 weeks, 300 μg/kg/day) restores the level of dopamine and its turnover in the striatum, leads to amelioration of motor dysfunctions, normalizes the mRNA levels of neurotrophin BDNF and inflammatory mediators TGFβ1, IL-1β and IFNγ in parts of the brain, and also normalizes the concentrations of steroids and inflammatory factors in the bloodstream. The peptide HLDF-6-H has therapeutic potential for the creation of a pharmaceutical drug on its basis for the treatment of PD.</p>