Objective: To investigate whether nerve mobilization related to nerve mobility or the removal of edema using lymphatic drainage affects the cross-sectional area of the nerve, hand function, and symptom severity in carpal tunnel syndrome. Design: The study is a prospective randomized controlled trial. Data were analyzed between groups using ANOVA, Chi-squared test, and Kruskal–Wallis test. Setting: Treatment lasted 4 weeks. Splint group wore the splint daily. Splint+manual lymphatic drainage received lymphatic drainage 5 days a week. Splint+nerve mobilization performed neuromobilization exercises as home exercises 5 days a week. Evaluations were conducted before and after 4 weeks of treatment. Participants: The study included 80 patients with mild-to-moderate carpal tunnel syndrome. Interventions: The patients were randomly divided into three groups: splint (n = 27), splint+manual lymphatic drainage (n = 27), or the splint+nerve mobilization (n = 26). Main Outcome Measures: The main outcome measures were ultrasound assessments and the Boston Carpal Tunnel Questionnaire (Symptom Severity Scale and Boston Functional Status Scale). Results: Compared to the other groups, the nerve cross-sectional area decreased at both the carpal tunnel (p = 0.003) and mid-forearm (p = 0.014) levels in the drainage group. Nerve mobilization did not result in a significant change in the nerve cross-sectional area. All groups showed significant improvements in both symptom severity and functional status scores (p < 0.001). Conclusion: The reduction of edema through lymphatic drainage contributes to a decrease in the cross-sectional area of the median nerve. Additionally, all three methods appear to positively impact the functional capacity of the hand and alleviate symptoms.