The influence of a course of medical treatment with the Semax nootropic peptide (50 and 200 μg/kg) on alcohol motivation and general behavior was studied in rats preliminarily alcoholized over six months. Semax was also included in the scheme of complex therapy of human alcohol dependence in clinical practice. Experiments with rats showed an increase in the locomotor and exploratory activity of rats and a decrease in the degree of depressive-like components. This effect compensated the behavioral changes observed in the control group exposed to alcohol deprivation. At the same time, the behavior of test groups under anxiogenic conditions showed increased anxiety. Semax in a dose of 200 μg/kg caused a significant increase in alcohol motivation, whereas its lower dose induced no proalcohol effect. Clinical trials demonstrated the safety (the absence of side effects and fairly high tolerance) of Semax in the course of alleviating the acute withdrawal syndrome and its efficacy for the recovery of mnestic functions (which was similar to the efficacy of Pyracetam). Semax did not change the frequency of cases of pathological craving for alcohol, but increased the overall intensity of behavioral reactions, which made the craving for alcohol stronger. These results allowed determination of safe course doses of Semax (to 50 μg/kg) under conditions of chronic alcoholization and inclusion of this nootropic agent in a scheme of complex therapy for patients with alcohol dependence. The mechanisms underlying the individual differences in the effects of Semax should be studied further.