Background Multiple sclerosis (MS) is a neurodegenerative disease with diverse symptoms, including autonomic nervous system impairment. While autonomic dysfunction is well-documented in MS, debate continues over its extent and whether it primarily affects the sympathetic or parasympathetic divisions. This review aimed to investigate heart rate variability (HRV) as an indicator of cardiac autonomic function in people with MS (PwMS)." Methods PubMed/MEDLINE, Web of Science, Embase, and Scopus were systematically searched up to August 2024 to identify observational studies that assessed HRV in PwMS and healthy controls (HCs). The standard mean difference (SMD) of HRV parameters, along with its 95% confidence interval (CI), between PwMS and HCs was estimated utilizing R version 4.4.0 within the random-effects model. Results This study combined data from 43 studies on 1518 PwMS and 1062 HCs. The meta-analysis revealed significant autonomic dysfunction in PwMS compared to HCs. Specifically, the time-domain measures such as root mean square of successive differences (RMSSD) (SMD = -0.81, p < 0.01) and pNN50 (SMD = -0.63, p < 0.001) showed significant reductions in PwMS, compared to HCs. Furthermore, among frequency domains, high frequency (HF) power (SMD = -0.51, p < 0.01) and low frequency (LF) power were significantly lower in PwMS (SMD = -0.44, p < 0.05) than HCs. Conclusion This review revealed that PwMS exhibited different HRV than healthy individuals. Additionally, HRV findings demonstrated greater sympathetic dominance in PwMS compared to healthy individuals. Future studies are needed to explore HRV in PwMS across varying severity levels, subtypes, and treatments to understand autonomic dysfunction in this population better.