Introduction: The interactions between Diabetes Mellitus type II (DMII) and Multiple Sclerosis (MS) lead to higher levels of fatigue, higher risk of physical disability, faster cognitive decline, and in general a lower quality of life and a higher frequency of depression compared to the general population. All of the above accelerate the disability progression of patients with MS, reduce the patients’ functional capacity, and further increase their psychological and economic burden. Methods: This systematic review and meta-analysis aims to calculate the prevalence of DMII in the MS population. Following PRISMA guidelines, a thorough search of the Medline Pubmed, Cochrane Library, and Scopus databases was performed, focusing on the frequency of DMII in the MS population. Results: A total of 19 studies were included in the synthesis. The results of the main meta-analysis of random effects using R studio 3.3.0 for Windows and the Meta r package showed that the prevalence of DMII in the MS population is 5% (95% CI [0.03, 0.07], 19 studies, I2 = 95%, pQ < 0.001). Additional subgroup analysis based on region showed a difference of 4.4% (I2 = 95.2%, pQ < 0.001), psubgroupdifference = 0.003) between European and non-European participants, while demographic- and MS-specific characteristic (EDSS, Disease Duration) did not seem to affect the prevalence of DMII in the MS population (p = 0.30, p = 0.539, p = 0.19, p = 0.838). No publication bias was discovered (Egger’s p test value: 0.896). Conclusions: Even though the prevalence of DMII in the MS population is lower than 10% (the reported prevalence of DMII in the general population) the interactions between the two conditions create significant challenges for MS patients, their caregivers, and physicians. DΜΙΙ should be systematically recorded in the case of MS patients to clearly delineate any potential relationship between the two conditions. Additionally, more structured studies investigating the interactions of MS and DMΙΙ as well as the direction of the causation between those two conditions are necessary in order to gain a deeper insight into the nature of the interaction between MS and DMII.