Introduction: Gamification has increasingly been incorporated into medical education to improve student engagement, motivation, and academic performance. By integrating game-related components, including points, rewards, leaderboards, and interactive challenges, gamification seeks to create a more engaging and student-centered learning environment. However, evidence regarding its effectiveness in improving knowledge acquisition and clinical competence among medical students remains inconsistent. This study aimed to systematically evaluate the effects of gamification-based learning interventions on knowledge outcomes, clinical skills, OSCE performance, and student motivation. Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Literature searches were performed in PubMed, Scopus, Google Scholar, and citation tracking sources through December 2025. Quantitative studies evaluating gamification interventions among undergraduate or professional medical students were included. Data were synthesized narratively, and meta-analysis was conducted using a random-effects model. Effect sizes were calculated using standardized mean differences with 95% confidence intervals, while heterogeneity was assessed using the I² statistic. Results: Fourteen studies met the inclusion criteria, and six studies were eligible for meta-analysis. The pooled analysis demonstrated a moderate positive effect of gamification compared with conventional teaching approaches. Greater benefits were observed in clinically oriented and skill-based learning activities, although substantial heterogeneity was identified across studies. Gamification also improved collaborative participation, learning satisfaction, and classroom interaction in several studies involving simulation-based educational activities among undergraduate medical education programs. Discussion: Gamification appears to be a promising educational strategy in medical education; however, additional high-quality studies are needed to establish more consistent evidence regarding its effectiveness across diverse educational settings.