Abstract Introduction Multiple Sclerosis (MS) severely affects strength, coordination, gait, and balance, leading to significant challenges for individuals. While exercise is known to benefit MS management, most studies focus on single modalities, leaving a gap in understanding the effects of combined training (CT) interventions. This systematic review aims to address this gap by examining the impact of diverse CT interventions on muscle strength, balance, gait speed, endurance, fatigue, and quality of life in people with MS (PwMS). The findings will provide valuable insights for enhancing rehabilitation strategies tailored to the multifaceted needs of PwMS. Methods Primary sources were gathered from eight databases: PubMed, SCOPUS, Embase, EBSCO, CENTRAL (Cochrane Central Register of Controlled Trials), CINAHL, PEDro, and Web of Science. The search timeframe ranged from the beginning of the study period until July 25, 2025. Quality assessment scores for the eligible studies were determined using the Physiotherapy Evidence Database (PEDro). Standardized mean differences (SMD), and 95% confidence intervals (CIs) were computed using either random or fixed models for the outcomes assessed. Results Following the screening process, 20 studies involving a total of 577 participants were included in the systematic review. The results of the meta-analysis showed that CT improved lower limb muscle strength (1.04 95% CI: 0.59–1.49, p = 0.001), balance (1.20 95% CI: 0.76–1.64, p = 0.001), gait speed (0.77 95% CI: 0.35–1.18, p = 0.001), gait endurance (0.96 95% CI: 0.46–1.46, p = 0.001), and quality of life (0.69 95% CI: 0.43–0.96, p = 0.001). Also, the results indicated that CT decreased fatigue (0.82 95% CI: 0.57–1.08, p = 0.001). Conclusion The systematic review and meta-analysis provide compelling evidence that CT interventions positively influence physical and functional outcomes in PwMS. Specifically, the results demonstrate significant improvements in muscle strength, balance, gait speed, gait endurance, and quality of life, alongside a notable reduction in fatigue. These findings underscore the potential of CT as an effective rehabilitation and management strategy for PwMS, suggesting that incorporating such interventions into clinical practice could enhance patient outcomes. By addressing key functional impairments and improving overall well-being, CT can play a crucial role in optimizing the quality of life for individuals living with multiple sclerosis, ultimately leading to more effective and holistic management of the condition. Registry number CRD420251111193
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