There is a strong body of evidence that supports the use of non-drug therapies in the management of people with multiple sclerosis (MS). A 5-day residential retreat for people with MS in Victoria, Australia, promotes lifestyle modification within a patient-centred model of care. Analysis of the health-related quality of life (HRQOL) of the retreat participants was undertaken using the MSQOL-54, prior to attendance, 1 and 5 years after the retreat. 274 retreat participants (71%) completed baseline questionnaires. Despite the usually progressive nature of MS, the cohort demonstrated clinically and statistically significant improvements in HRQOL. One year after attending the retreat, median improvements of 11.3% were observed in the overall quality of life domain (p < 0.001); 18.6% in the physical health composite (p < 0.001); and 11.8% in the mental health composite (p < 0.001). In the subset of 165 who had reached the 5-year time-point, there was a 19.5% median improvement in overall quality of life (p < 0.001); 17.8% in the physical health composite (p < 0.001) and 22.8% in the mental health composite (p < 0.001), compared to baseline. Attendance at a retreat promoting lifestyle modification for the integrated management of MS appears to have positive effects on short and medium-term HRQOL. Non-drug therapies should be considered as part of any comprehensive treatment plan for people with MS.