Depression and anxiety are the leading causes of disability in the United States among people aged 18 to 25. Protective factors such as self-esteem, grit, and optimism may help individuals manage depression and anxiety. The present study aimed to understand the role of these factors as predictors of depressive and anxiety symptoms in emerging adults. A sample of 3,413 students completed instruments measuring grit, self-esteem, optimism, depression, and anxiety. Application of the hierarchical regression model indicated that self-esteem, grit, and optimism significantly negatively predicted depression and anxiety in the students. Additionally, self-esteem accounted for the maximum variance in depression ([beta] = -0.45) and anxiety ([beta] = -0.35) as compared to grit ([beta] = -0.13; [beta] = -0.06) and optimism ([beta] = -0.14; [beta] = -0.18). These findings reinforce the importance of exploring protective factors that may buffer against depression and anxiety among college students. The results of this study also have implications for future research in terms of understanding the mechanism of how self-esteem, grit, and optimism are differently linked to depression and anxiety.