BackgroundAffective disorders are becoming more pervasive worldwide, including in Southern Africa, where treating patients with these conditions is challenging due to social and financial constraints. A variety of non-pharmacological approaches including lifestyle medicine (e.g., exercise, nutrition, sleep) and positive psychology practices (e.g., gratitude, service), are effective for treating mental health (MH) conditions.MethodsTwenty-six individuals from South Africa with a diagnosed MH condition participated in a 10-week multimodal intervention incorporating a diverse range of non-pharmacological strategies for improving MH. MH metrics were assessed pre-and post-intervention, including general MH, vitality/energy (VIT), depression, anxiety, stress, and satisfaction with life. MH and VIT were also measured weekly.ResultsImprovements were observed in all mental metrics from pre-to post-intervention: MH (59%, p < 0.001, Cohen’s D = 1.36), VIT (110%, p < 0.001, Cohen’s D = 1.71), depression (−46%, p < 0.001, Cohen’s D = −1.06), anxiety (−48%, p < 0.001, Cohen’s D = −1.21), stress (−36%, p < 0.001, Cohen’s D = −1.08) and life satisfaction (23%, p < 0.001, Cohen’s D = 0.66). Significant improvements in MH and VIT were observed after only 1 week of the intervention and progressively increased until the seventh week, after which further improvements were not statistically significant.ConclusionThe findings of this cohort study indicate that a multimodal intervention that incorporates lifestyle and positive psychology practices may benefit individuals living with an affective disorder. Non-pharmacological, multimodal interventions might offer a stigma-free way of providing MH promotion and treatment at a population level.