Introduction: This meta-analysis investigates the effects of Vitamin D and Vitamin B6 supplementation on premenstrual syndrome (PMS) in adolescents, with a specific focus on their impact on physical fitness and participation in games and sports. Methodology: A comprehensive literature searches up to March 2022 identified 11 trials involving 1456 participants. Among these, 745 were diagnosed with PMS, and 711 served as controls. The study aimed to elucidate the relationship between Vitamin D and Vitamin B6 supplementation and PMS. The analysis was conducted using continuous and dichotomous methods within fixed and random-effect models, depending on heterogeneity, to calculate odds ratios (OR) with 95% confidence intervals (CIs). Results: Vitamin B6 supplementation was significantly associated with reduced PMS scores compared to the control group (OR, -10.22; 95%CI, -15.49 to -4.95), suggesting a potential positive impact on adolescents' physical fitness and ability to participate in games and sports. However, Vitamin D levels did not show a significant correlation with PMS improvement (OR, -4.55; 95%CI, -9.70 to 0.60). Conclusions: The administration of Vitamin B6 has shown a significant improvement in PMS symptoms and scores in adolescents, potentially enhancing their physical activity and game participation. In contrast, Vitamin D did not demonstrate a significant effect on PMS. These findings underscore the potential role of Vitamin B6 in managing PMS symptoms in adolescents and its positive implications for their physical engagement and overall well-being.