<p>Symptoms of anxiety, depression, fatigue, and decreased quality of life are common in patients with multiple sclerosis and web-based psychological treatments may help to improve such symptomatology. Therefore, the aim of this research was to perform a systematic review and meta-analysis on the efficacy of web-based psychological interventions to improve these symptoms in patients with multiple sclerosis. We selected randomized or non-randomized clinical trials with adult population diagnosed with multiple sclerosis, treated with web-based psychological treatments, providing a comparative group with similar clinical characteristics to the intervention group, and providing measures of anxiety, depression, fatigue, or quality of life. The search was conducted in seven databases in December 2023. Publication bias was assessed with Egger’s test, Hedges’ <i>g</i> effect size was calculated, and meta-regression analyses were performed. Eighteen studies were included, with 25 treatment groups and 14 comparative groups. Effect sizes were of moderate magnitude, and somewhat lower but less heterogeneous when treatments were exclusively cognitive behavioral. Higher effect sizes were found when treatments were of short duration, incorporated relaxation components, goal setting, and physical activity, and were applied early. Cognitive behavioral web-based psychological treatments are a recommended choice for the treatment of these symptoms in patients with multiple sclerosis.</p>