The diagnosis and quantification of Multiple Sclerosis (MS) have typically depended on skilled doctors recognizing visual patterns, such as Magnetic Resonance Imaging (MRI) and Electroencephalography (EEG), which resulted in a costly, time-consuming and non-reproducible process. The application of Machine Learning (ML) in MS diagnosis has been getting a lot of attention in the last few years due to the volume of scientific data, the heterogeneity of disease courses, and the variety of diagnostic methods. The EEG has the capability to detect important changes in the brain’s inherent electrical activity, which are influenced by changes in the neural network connections associated with inflammatory demyelinating and neural damage characteristic of the MS. Utilizing multimodal machine learning over the clinically available data may be a contemporary strategy with amazing potential to facilitate early diagnosis. Considering recent EEG investigations as well as the accessibility to their datasets would be the initial steps in utilizing the ML in MS diagnosis. This paper provides a systematic review of the latest techniques for MS diagnostic based on PRISMA guidelines with the prospect of ML application in their investigations. The goal is to find if EEG could be considered a robust and accurate technique for MS diagnosis. In accordance with PRISMA guidelines, we consider 111 papers. In our review, 404 people are considered including 209 with MS and 195 healthy controls. As a result, we generated an updated investigation looking at the ML approaches as well as utilizing EEG as an accurate, but less often used method to help with early diagnosis of MS. We summarize, analyze, discuss, and synthesize the recently published works, current trends, and open research issues. The review also points out knowledge gaps about the necessity of validating results and addressing constraints such as limited sample number. Our investigation proves that the precision of the supervised strategies such as [Formula: see text]NN and SVM is typically higher than that of the unsupervised strategies. On the other hand, by utilizing various techniques such as splitting EEG signal sub-bands, signal windowing, and identifying effective features from the data analysis approaches, we have been able to achieve significant classification accuracy higher than 99%. According to the high degree of accuracy of the results, this approach is becoming the focal point of the research works. The high diagnostic accuracy of the proposed machine learning techniques on the EEG signal analysis shows its potential capacity to become a more widespread procedure as the MS diagnostic techniques. To develop the reliability of these methods, gathering, and analyzing more EEG signals from MS patients and creating more suitable EEG protocols are essential in future studies. In the same way, for the dynamic and online analyses of the EEG signals, in-depth studies are needed to determine more effective EEG protocols and machine-learning techniques.