This study examined the effectiveness of a 10-week multimodal intervention for improving the mental health and emotional well-being of college students when included as a mandatory component of the students’ course of study. A total of 67 students (20.9 ± 5.4 years, 30 male/37 female) participated in the intervention that introduced a variety of evidence-based strategies for improving mental health and emotional well-being from the Lifestyle Medicine and Positive Psychology literature. Significant reductions were recorded in symptoms of depression (−28%, P < .05), anxiety (−31%, P < .05), and stress (−28%, P < .01), whereas significant improvements were observed in mental health (18%, P < .01), vitality (14%, P < .01) and overall life satisfaction (8%, P < .05). Effect sizes were larger than those reported by studies that have examined the individual effectiveness of the strategies incorporated into the intervention, suggesting a compounding effect. Stratified analyses indicated that participants with the lowest measures of mental health and emotional well-being at baseline experienced the greatest benefits. The findings of the study suggest that meaningful improvements in the mental health and emotional well-being of college students can be achieved, and potentially magnified, by utilizing a multidisciplinary approach involving evidence-based strategies from Lifestyle Medicine and Positive Psychology.