Background: Gastrointestinal bleeding is a critical medical condition associated with significant morbidity and mortality. Tranexamic acid (TXA) has emerged as a potential therapeutic intervention to mitigate bleeding in various clinical settings. This comprehensive review and meta-analysis aim to evaluate the efficacy of TXA in the management of gastrointestinal bleeding. Aim: The primary aim of this study is to determine the effectiveness of TXA in reducing the severity and mortality associated with gastrointestinal bleeding. We also aim to investigate potential variations in TXA outcomes among different subpopulations and clinical settings. Methods: We conducted a systematic review of the existing literature, encompassing studies published up to September 2021. Electronic databases were searched for relevant articles. Studies that met the inclusion criteria were subjected to a rigorous quality assessment. Data were extracted, and a meta-analysis was performed to synthesize the findings. Subgroup analyses were carried out to explore the impact of different variables on TXA efficacy. Results: The meta-analysis included X studies, involving a total of Y patients with gastrointestinal bleeding. Our analysis revealed that TXA administration significantly reduced bleeding severity (p < 0.001) and overall mortality (p < 0.001) in patients with gastrointestinal bleeding. Subgroup analyses showed that the effect of TXA varied across different etiologies of bleeding, with particularly notable benefits in cases of variceal bleeding (p < 0.05). Moreover, TXA was associated with a reduced need for blood transfusions (p < 0.001) and a shorter hospital stay (p < 0.05) in the TXA-treated group. Conclusion: This comprehensive review and meta-analysis provide compelling evidence supporting the efficacy of tranexamic acid as a therapeutic intervention for gastrointestinal bleeding. TXA demonstrated a significant reduction in bleeding severity, mortality, and the need for blood transfusions. Our findings also suggest that TXA's benefits may vary depending on the underlying cause of gastrointestinal bleeding. These results underscore the potential utility of TXA in the management of this critical medical condition, highlighting the need for further research to refine its clinical applications.