Background <p>Previous studies indicate that physical activity significantly alleviates anxiety among college students, and that psychological resilience and social support may mediate this relationship; however, existing evidence remains limited. This study aims to examine the mediating roles of psychological resilience and social support in the relationship between physical activity and anxiety in college students, and to analyze potential moderating factors.</p> Methods <p>Eight databases were searched without restrictions on language or publication time to obtain relevant coefficients. Meta-analytic structural equation modeling (MASEM) was applied to verify the mediating roles of psychological resilience and social support. In addition, one-stage MASEM was employed to assess the moderating effects of female proportion and sampling methods.</p> Results <p>Twenty-nine articles were included, comprising a total sample of 36,159 participants and 90 effect sizes. Physical activity had a significant negative effect on college students’ anxiety (β = –0.262, 95% CI: –0.281, –0.243). Psychological resilience (β = –0.152, 95% CI: –0.163, –0.142) and social support (β = –0.048, 95% CI: –0.055, –0.042) served as mediators. Female proportion and sampling methods exhibited moderating effects on the model. Sensitivity analysis and publication bias tests supported the robustness of the findings.</p> Conclusion <p>Increasing college students’ physical activity levels effectively reduces anxiety, and physical activity indirectly alleviates anxiety through enhanced psychological resilience and social support. Future research should focus on causal relationships among variables and on differential effects of gender and sampling methods, thereby providing more effective mental health support for college students.</p> Trial registration <p>This study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD420251129622).</p>