While prior research has shown higher mindfulness is associated with lower problematic smartphone use (PSU), the contexts of these studies were not related to education or student performance. As such, whether and how mindfulness can reduce the adverse effects of PSU on academic self-efficacy remains unknown. This study proposed a model for testing whether and how mindfulness exerts its effects on PSU and academic self-efficacy through different pathways in which self-esteem, academic motivation, and smartphone time serve as mediators. To this end, a questionnaire survey, comprising Smartphone Addiction Scale (Short Version), Mindful Attention Awareness Scale, Short Academic Motivation Scale, Rosenberg Self-esteem Scale, and Educational Self-efficacy Scale, was administered to a sample of 821 university students from Hong Kong during the COVID-19 pandemic in 2022. The findings of this study show that mindfulness reduces the adverse effects of PSU on academic self-efficacy. Four different mediation pathways were identified, showing how the effects of mindfulness on PSU and academic self-efficacy are mediated through self-esteem, academic amotivation, and smartphone time. Specifically, mindfulness has a direct negative effect on PSU and a direct positive effect on academic self-efficacy. Mindfulness also exerts indirect effects on PSU mediated serially by self-esteem, academic amotivation, and smartphone time.