During last years, alpha-ketoglutarate (AKG), an important intermediate in the Krebs cycle, has been intensively studied as a dietary supplement with stress-protective and potential antiaging effects. Here, we examined the effects of exogenous AKG on metabolic processes and survival of yeast Saccharomyces cerevisiae during long-term cultivation. Growth on AKG had no effect on the total cell number but increased the number of reproductively active cells at the late days of cultivation (from day 7 to day 15). A gradual increase in levels of total protein, glycogen, and trehalose was found over 7-day cultivation with more pronounced effects in AKG-grown cells. In control cells, metabolic activity and the activities of superoxide dismutase and catalase decreased, whereas levels of carbonyl proteins and low-molecular-mass thiols increased during 7-day cultivation. This suggests development of oxidative stress in stationary phase cells. Meanwhile, stationary phase cells cultured on AKG possessed higher levels of low-molecular-mass thiols and lower levels of carbonyl proteins and α-dicarbonyl compounds when compared to control ones. Collectively, higher levels of storage carbohydrates and an activation of antioxidant defense with diminishing oxidative protein damage can prevent a loss of reproductive ability in yeast cells during long-term cultivation on AKG-supplemented medium.