Carpal Tunnel Syndrome (CTS) represents the most common compressive mono-neuropathy of the upper limbs and leads to significant disability. Aim: This study aimed to evaluate the efficacy of manual therapy interventions on symptoms severity and functional status in patients with CTS. Design: A pretest and post-test quasi-experimental research design was used. Setting: This study was conducted in Outpatient Clinic of departments of Brain and Neurology, affiliated to Zagazig University Hospitals. Sample: A Purposive sample of 50 adult patients with diagnosis of mild to moderate CTS. Tools: A Structured Interview Questionnaire for Patients with Carpel Tunnel Syndrome, Boston Carpal Tunnel Questionnaire (BCTQ), and Patient-Rated Wrist Evaluation (PRWE) Questionnaire. Results: There was significant improvement in symptoms severity and functional status post- manual therapy interventions with mean scores 58.18 ± 15.0 & 33.9 ± 10.21 respectively at p- value < 0.001. There was a highly statistically significant difference regarding patient-rated wrist evaluation at pre- and post-manual therapy interventions with mean scores 70.17 ± 11.97& 30.92 ± 9.13 respectively at p- value < 0.001. Conclusion: According to the study findings, it can be concluded that application of manual therapy interventions for patients with CTS had a statistically significant effect on improving symptoms severity, functional status, wrist pain, and functional disability in activities of daily living, which supported the proposed hypotheses. Recommendations: Further research on larger probability sample is recommended to compare different combinations of manual therapy interventions in management of CTS.