Multiple sclerosis (MS) is a chronic, degenerative autoimmune inflammatory disease of the central nervous system. MS is characterized by a wide range of symptoms and unpredictable prognosis, which can severely affect patient quality of life (QOL). The treatment strategy includes acute relapse treatment, disease-modifying treatment (DMT), and symptomatic therapy. Adherence to long-term DMTs is essential in order to maximize the therapeutic effects for MS and is crucial to health-related quality of life (HRQOL). This study aimed to evaluate the relationship between QOL and adherence to DMTs in MS patients. A group of 344 patients (73% females) aged 39.1 years with relapsing-reemitting MS were included. The Multiple Sclerosis International Quality of Life (MusiQOL) and the Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ) were used. An injection of interferon (IFN)-β1b was used in 107 patients, IFN-β1a in 94 patients, and glatiramer acetate in 34 patients. The oral treatment includes teriflunomide in 14 patients, dimethyl fumarate in 86 patients, and fingolimod in nine patients. No statistically significant differences (p > 0.05) were observed in adherent (ADH) vs. non-adherent patients (non-ADH) in MusiQOL. The total adherence rate was 72% (MS-TAQ). An analysis of the univariate logistic regression model showed an effect of only the activities of daily living (ADL) and relationship with the healthcare system (RHCS) domains on the level of adherence to treatment recommendations. The other variables studied do not affect the level of adherence. Higher QOL levels in the ADL and RHCS domains affect medication adherence in MS patients. Our findings could help manage MS patients, promoting interventions on ADLs and good relationships with healthcare providers to improve their adherence to therapy and result in better QOL.