Physical activity (PA) decreases during the transition from childhood to adolescence, with larger declines observed in girls. School-based interventions are considered the most promising approach for increasing adolescents' PA levels although, it is unclear which types of school-based interventions have the greatest impact. The objective of this systematic review is to assess the impact and design of school-based PA interventions targeting adolescent girls. A systematic search was conducted using four electronic databases (PubMed, Web of Science, SPORTDiscus and PsychInfo). This systematic review was registered with PROSPERO (Registration number: CRD42016037428) and PRISMA guidelines (2009) were followed throughout. Twenty studies were identified as meeting the inclusion criteria and were included in a narrative synthesis. Seventeen studies were eligible for inclusion in a meta-analysis. There was a significant small positive treatment effect for school-based PA interventions for adolescent girls (k=17, g=0.37, p<0.05). After an outlier was removed (residual z=7.61) the average treatment effect was significantly reduced, indicating a very small positive effect (k=16, g=0.07, p=0.05). Subgroup analysis revealed very small significant effects for multi-component interventions (k=7, g=0.09, p<0.05), interventions underpinned by theory (k=12, g=0.07, p<0.05), and studies with a higher risk of bias (k=13, g=0.09, p<0.05). Intervention effects were very small which indicates that changing PA behaviors in adolescent girls through school-based interventions is challenging. Multi-component interventions and interventions underpinned by theory may be the most effective approaches to positively change adolescent girls' PA.