Objectives: This study aimed to evaluate adherence to disease-modifying therapies (DMTs) among patients with multiple sclerosis (MS) and to identify factors influencing compliance, based on perceptions and preferences of both patients and neurologists. Methods: Questionnaires were designed by a team of experts, including MS specialists, psychologists, and statisticians, to capture data on treatment adherence and related factors. A total of 1021 MS patients and their neurologists participated. Patients' adherence to oral, injectable, and infusion DMTs was assessed alongside demographic and disease-related characteristics. Results: The study included 1021 MS patients with a mean age of 35.69 ± 9.07 years. Infusion therapies demonstrated the highest adherence rates (96.6%). Among all patients, 78.9% maintained treatment without interruption, while 56.7% of those who interrupted therapy informed their physicians. Patients with a disease duration of less than one year or more than 10 years exhibited lower rates of treatment interruption compared to those with a disease duration of 1–10 years (p = 0.032). In the injectable DMT group, significant differences in adherence were noted (p < 0.001). The lowest interruption rate (13.5%) was seen in patients with a disease duration of less than one year, whereas interruption rates were markedly higher (83%) in those with a duration exceeding 16 years. Conclusion: Improving adherence requires a patient-centered, collaborative approach emphasizing shared decision-making between physicians and patients. Addressing factors that contribute to non-compliance is essential for optimizing treatment outcomes and enhancing long-term disease management in MS.