Background: Subjective well-being (SWB) can be a buffer against mental health problems. Patients with multiple sclerosis (MS) tend to experience low levels of subjective well-being. Objectives: The two objectives were (1) to examine whether peer-led and nurse-led self-management training can improve SWB of patients with MS and (2) to compare the effect of these two interventions on SWB of patients with MS. Methods: In this trial, 81 patients were randomly assigned to either nurse-led (n = 41) or peer-led (n = 40) groups. Both groups participated in six weekly-based 1.5‐hr self-management sessions. The cognitive and affective components of SWB were evaluated using the Satisfaction with Life Scale and the Scale for Positive and Negative Experience, respectively. Results: Life satisfaction increased in both groups over time (P < 0.001), although it was not significantly different between the two groups (P > 0.05). Positive and negative experiences increased in both groups over time (P < 0.05), but the increase in positive experience in the peer-led group was significantly larger than those in the nurse-led group (P < 0.05). Conclusions: Peer-led and nurse-led self-management training, are feasible tools to enhance the cognitive component of SWB, i.e., life satisfaction. Considering the affective component of SWB, positive experience in the peer-led group improved better than in the nurse-led group over time. Therefore, if healthcare providers improve the SWB of patients with relapsing-remitting MS, the self-management intervention led by peers is preferred than nurse-led self-management training.