Background/Objectives: Ischemic stroke remains a leading cause of death and disability worldwide. Despite significant progress in reperfusion therapy, the optimal ischemic stroke management strategy has not been developed. Recent studies demonstrate that microRNA may play an essential role in the pathophysiology of ischemic stroke and its possible potential to be a treatment target point. The proposed systematic review aimed to report the relationship between IS’s clinical severity and miRNA expression. Secondary outcomes included infarct volume, systemic inflammatory markers, and prognosis, as well as additional features such as stroke subtype, comorbidity, and risk of subsequent stroke in correlation to miRNA expression. Methods: We have performed a systematic search of database resources according to PRISMA statement guidelines. Twenty-seven studies on a total number of 3906 patients were assessed as suitable for the present SR. Included studies analyzed the expression of 30 different miRNA fragments. Results: After investigating available data, we have identified a set of possible miRNA fragment candidates that may be used in stroke diagnostics and have the potential to be a base for the development of future treatment protocols. Conclusions: Studies included in the presented SR indicate that miRNA expression may be significantly associated with clinical severity, infarct volume, and inflammation in ischemic stroke. More prospective, properly designed protocols with consistent methods of miRNA testing and optimized clinical assessment are needed to confirm the role of miRNA expression in the course of a stroke.