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Background The mental health problem of college students has become an increasingly prominent public health problem. Mindfulness exercise (ME) is considered to be a promising way to improve psychological well-being. However, the underlying mechanisms by which mindfulness exercise affects mental health (MH) remain poorly understood. Based on the theory of self-regulation, this research explores the sequential mediating role of sleep regularity (SR) and self-control (SC) in the relationship between mindfulness exercise and mental health of college students. Methods A cross-sectional survey was conducted among 470 Chinese undergraduate students using validated self-report instruments measuring mindfulness exercise, sleep regularity, self-control, and mental health. Data were analyzed using partial least squares structural equation modeling (PLS-SEM) with SmartPLS 4.1. Measurement reliability and validity were assessed, and bootstrapping procedures (5,000 resamples) were employed to test direct, indirect, and sequential mediation effects. Results The measurement model demonstrated satisfactory reliability, convergent validity, and discriminant validity. Structural model results indicated that mindfulness exercise was positively associated with sleep regularity ( β = 0.457, p < 0.001), sleep regularity was positively associated with self-control ( β = 0.288, p < 0.001), and self-control was positively associated with mental health ( β = 0.296, p < 0.001). Mediation analyses revealed that sleep regularity significantly mediated the relationship between mindfulness exercise and self-control, while self-control mediated the association between mindfulness exercise and mental health. Moreover, a significant sequential mediating effect of sleep regularity and self-control was observed in the relationship between mindfulness exercise and mental health. Conclusion Mindfulness exercise was positively associated with MH among university students, and this association was linked to sleep regularity and self-control. The results enhance the theoretical understanding of the behavioral and self-regulation mechanisms linking mindfulness exercise and mental health, and provide practical implications for the development of integrated mental health promotion interventions targeting sleep behavior and self-regulation in higher education environments.