Objective: To examine the effects of mindfulness- and acceptance-based interventions (MABIs) on reducing symptoms in individuals with multiple sclerosis (MS). Data Sources: A comprehensive search was conducted within the PubMed, CINAHL, PsycINFO, and SCOPUS databases for articles published from inception to July 3, 2020. Study Selection: Randomized controlled trials (RCTs) were included if MABIs were provided to individuals with MS exclusively, with reported pre-and posttest results in symptoms of depression, anxiety, stress, fatigue, or pain. Data Extraction: Characteristics of the included RCTs and data for meta-analysis were extracted. The quality of the included RCTs was assessed using the Cochrane Collaboration risk of bias tool. Data Synthesis: A random effects model with the inverse variance method was used with effect size reported as standardized mean difference. Heterogeneity was assessed using the I2 statistic. Results: Twenty-three RCTs met the eligibility criteria. Meta-analyses found large effects of MABIs on reducing depressive symptoms, anxiety, stress, and pain, as well as a moderate effect of MABIs on reducing fatigue at the immediate posttest. Large effects of MABIs on reducing depressive symptoms, anxiety, and stress at follow-up were also found, whereas a moderate effect on reducing fatigue was found at follow-up. There was no significant effect of MABIs on reducing pain at follow-up. Conclusions: Fewer studies were included in meta-analyses for pain at the immediate posttest and follow-up and stress and fatigue at follow-up. The overall risk of bias was unclear. Future high-quality studies with follow-up evaluations are needed to support effects of MABIs on reducing symptoms in individuals with MS and examine intervention features that increase and maintain effects.