Positive psychology is a useful framework to understand Mexican American college students’ complete mental health. In the current study, we examined how presence of meaning in life, search for meaning in life, hope, mindfulness, and grit influenced 130 Mexican American college students’ life satisfaction and depression. Within the first regression model, hope, mindfulness, and presence of meaning in life were positively related with life satisfaction. Within the second regression model, mindfulness and search for meaning in life were related with depression. Higher levels of mindfulness negatively predicted depressive symptoms, while higher levels of search for meaning in life were related with higher levels of depressive symptoms. A discussion regarding the importance of these findings and recommendations for future research are provided.