Previous studies have suggested that omega-3 polyunsaturated fatty acids, predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have several health benefits. However, their effect on changes in skeletal muscle mass and strength has not been established, owing to differences in study designs. This systematic review aimed to investigate the recent evidence regarding the role of dietary EPA and DHA in muscle mass changes and their association with muscle strength. Databases including PubMed and Google Scholar were searched for randomized controlled trials and single-arm interventions that investigated the effects of omega-3 fatty acids on skeletal muscle mass, strength, and body composition in adults aged 18 years and older. A total of 18,521 studies were retrieved from the databases and manual searches; 21 studies were quality assessed, and the findings were summarized. Studies were categorized into 3 main categories according to the type of omega-3 fatty acid supplementation: pure compounds such as oil tablets, formulated forms with protein, leucine, and vitamin D, and ingredients added to enteral nutrition support products. Overall, the majority of the study results appeared to indicate that omega-3 fatty acids are beneficial for muscle health. However, meta-analysis was not conducted because of the heterogeneity of the study participants, evaluation method of muscle indices, and intervention periods among the studies. High-quality studies are required to validate our conclusions. However, this systematic review of the effects of EPA and DHA on skeletal muscle and body composition provides evidence that can be applied in both clinical and industrial settings.