<p>Mental health is the cornerstone of comprehensive development and healthy growth of college students, and a key factor in determining personal achievement and well-being. Physical activity, as a core carrier of education, has a unique value and function in promoting mental health. This study explored the associations of physical activity on college students’ mental health and the mediating roles of smartphone addiction and perceived social support between the two. A convenience sampling method was used to survey 3466 college students using the Physical Activity Rating Scale, Depression-anxiety-stress Scale, Smartphone Addiction Scale, and Perceived Social Support Scale, and structural equation modelling and Bootstrap methods were used to conduct mediation tests and effect analyses of smartphone addiction and perceived social support. ① There was a negative correlation between physical activity and depression-anxiety-stress (<i>r</i>=-0.337, <i>P</i> &lt; 0.001), which was a significant direct association with depression-anxiety-stress. ② Physical activity was negatively associated with smartphone addiction, positively associated with perceived social support (<i>r</i>=-0.568, <i>r</i> = 0.091, <i>P</i> &lt; 0.001), smartphone addiction was negatively associated with perceived social support and positively associated with depression-anxiety-stress (<i>r</i>=-0.272, <i>r</i> = 0.593, <i>P</i> &lt; 0.001), and perceived social support was negatively associated with depression-anxiety-stress (<i>r</i>=-0.381, <i>P</i> &lt; 0.001), ③ Smartphone addiction and perceived social support demonstrated a significant statistical mediation pattern in the association between physical activity and depression-anxiety-stress. The three paths of mediation effect were as follows: Path 1: Physical activity → smartphone addiction → depression-anxiety-stress, with a mediation effect value of -0.076, 95% CI=[-0.078, -0.071], and the mediation effect accounted for 80.85% of the total effect. Path 2: Physical activity → perceived social support → depression-anxiety-stress, with a mediation effect value of -0.005, 95% CI=[-0.008,-0.002], and the mediation effect accounted for 5.32% of the total effect. Path 3: Physical activity → smartphone addiction→ perceived social support → depression-anxiety-stress, the mediating effect value was − 0.013, 95% CI [-0.015, -0.010], the mediating effect accounted for 13.83% of the total effect. ① Physical activity is significantly negatively correlated with depression-anxiety-stress levels in university student, ② There is a statistical mediation pattern in which physical activity is associated with depression-anxiety-stress among college students through smartphone addiction and perceived social support, respectively, ③ A statistical serial mediation pattern through smartphone addiction and perceived social support was observed for the effect of physical activity on depression-anxiety-stress in the student sample.</p>