The Genome-based Mexican (GENOMEX) diet is a strategy for preventing and managing obesity. Emotion and eating behavior in the context of a nutrigenetic intervention have not been thoroughly studied. We aimed to explore the influence of the GENOMEX diet on emotions, self-efficacy, and rewarding behaviors in unhealthy eating among subjects with risk factors for obesity-related chronic diseases. Twenty-eight subjects included in the six-month GENOMEX intervention answered questions regarding emotions that influence food consumption. Additionally, the Patient Health Questionnaire (PHQ-9) and the Reward-based eating drive scale (RED) were applied. In the study, minimal, mild, moderate, and severe depression were present in 46.4%, 39.3%, 10.7%, and 3.6%, respectively. RED did not change, but it correlated with a higher intake of fats (r2 = 0.684, β = 2.066, p = 0.003). Mood influenced unhealthy eating in 71.7% of subjects, and 76.9% experienced binge episodes triggered by anxiety. Sugars were the most consumed foods during binge episodes (42.2%). Both low self-efficacy levels and binge episodes were associated with high consumption of unhealthy foods. After the intervention, 10.7% of subjects reported a high level of self-efficacy. In conclusion, a culturally acceptable and genetically compatible regional Mexican food diet reduced negative emotions and unhealthy eating while increasing self-efficacy.