Red Ginseng Extract (RGE) is known to have various health benefits such as fatigue relief and tonicity. However, the effects of RGE on intracellular energy metabolism are not well understood. In this study, we treated HK-2 cells, a human proximal tubular cell line, with RGE and examined the effects on cell proliferation and changes in intracellular metabolites. First, RGE was found to promote cell proliferation in HK-2 cells in a concentration-dependent manner; LC-MS/MS analysis revealed that RGE significantly increased intracellular pantothenate, proline, and glutathione levels. In contrast, extracellular (culture medium) pantothenate levels decreased in a RGE concentration-dependent manner, suggesting that RGE enhances intracellular uptake of pantothenate. Pantothenate is synthesized intracellularly to coenzyme A (CoA), which is then converted to acetyl CoA and involved in various intracellular events, including energy metabolism. We found that inhibition of the synthesis of coenzyme A from pantothenate inhibited the effect of RGE on HK-2 cell proliferation. These results suggest that RGE activates cell proliferation via an increase in intracellular pantothenate levels and is involved in the activation of antioxidant effects and energy metabolism. Next, we investigated the protective effect of RGE during nutrient starvation in HK-2 cells. The results showed that RGE abrogated intracellular stress signals and inhibited cell death in HK-2 cells during acute nutrient starvation. Collectively, our results suggest that RGE acts as a regulator of intracellular energy metabolism under both nutrient and starvation conditions.