Yeast accumulate glycogen as a major carbon and energy reserve to buffer against environmental starvation conditions. Glycogen is a branched polysaccharide of glucose that is initiated from glycogenin, a self-glucosylating priming protein. There are two homologs of glycogenin in human and yeast, Glg1p and Glg2p, both of which are capable of priming glycogen synthesis. While Glg1p and Glg2p have distinct sequence characteristics, differences in their molecular function and physiological roles have not been investigated. Here, we created yeast strains lacking either or both glycogenins, either genetically deficient or complemented. Analysis of glycogen content showed differences between these yeast strains depending on the presence of Glg1p or Glg2p. We then performed global SWATH-MS analysis of these strains, which identified large and significant changes in their proteomes. In particular, we identified changes in central carbon metabolism, protein stress response, and trehalose regulation. Our results support a critical role for glycogen in general stress response beyond a carbon storage molecule, and suggest different specific functions for Glg1p and Glg2p.