Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. MS manifests in a wide range of motor, sensory and other symptoms including fatigue, pain, and cognitive impairments, which may have significant negative impacts on quality of life (QoL). Mindfulness-Based Interventions (MBIs) have been shown to safely improve MS-specific predictors of reduced QoL, including fatigue, anxiety, stress, and depression, in people with MS (pwMS). However, the efficacy and long-term effects of MBIs on QoL, remain unclear. Objectives: To systematically review the literature for evidence for the effectiveness of MBIs on QoL in pwMS and the long-term effects. Methods: EMBASE, PsycINFO, and Medline were searched for studies, published from database inception to 2020, that assessed the association of MBIs on QoL in pwMS. Randomized controlled trials (RCTs), quasi-RCTs, and observational studies were included. Study quality was assessed using Cochrane Collaboration Risk of Bias tools. Results: Of 181 studies identified, seven met the inclusion criteria; five were high-quality RCTs with moderate risks of bias, and two were observational studies with serious risks of bias. Three studies adopted non-active control, three used active control, and one had no control comparison. Interventions and QoL tools varied across studies, the most common being mindfulness- based stress reduction and multiple sclerosis quality of life - 54, respectively. All studies measured QoL pre- and immediate post-intervention. The follow-up periods were between 3-12 months in RCTs. Six of seven studies found MBIs improved overall QoL from baseline to post-intervention. Four studies additionally reported improved mental health QoL, and one reported improved physical QoL. RCTs assessed long-term effects, of which only three reported lasting positive effects of up to 12 months. Conclusions: This review is the first to investigate the long-term effect of mindfulness in pwMS on QoL. It provides further evidence that MBIs are valuable methods to improve overall and mental health QoL in pwMS, effects which may be long-lasting. The differences in long term-effects may be due to many things, including adherence of mindfulness self-practice among pwMS. Future studies using consistent QoL tools and monitoring intervention adherence are needed.