Background: Carpal Tunnel Syndrome (CTS) is a common condition characterized by compression of the median nerve, leading to pain, numbness, and hand dysfunction. Both manual therapy and surgical decompression are widely used interventions, but their comparative effectiveness remains uncertain. Methods: A systematic review and a meta-analysis were conducted to compare the short- and long-term efficacy of manual therapy versus surgery for CTS. Studies were selected based on randomized controlled trials (RCTs) that met the inclusion criteria, focusing on outcomes such as pain intensity, hand function, symptom severity, and quality of life. Data were extracted and analyzed by using standardized tools to assess treatment effects. Results: Five RCTs with a total of 533 participants were included. Manual therapy was more effective for short-term pain relief, with significant improvements at 1 and 3 months compared with surgery. However, at 6 to 12 months, surgical intervention provided greater improvements in hand function and symptom severity. Quality-of-life improvements were similar in both groups. Risk of bias was moderate to low across the studies, with limitations in blinding due to the nature of the interventions. Conclusions: Manual therapy offers effective short-term relief for CTS, making it a viable option for patients with mild to moderate symptoms. Surgery provides more durable, long-term outcomes, particularly for severe cases. The choice of treatment should be individualized, considering patient preferences and symptom severity.