Stroke is known as one of the very important public health problems that are related to societal burden and tremendous economic losses. It has been shown that there are few therapeutic approaches for the treatment of this disease. In this regard, the present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neuro recovery. Among these therapies, regenerative medicine-based therapies have appeared as new ways of stroke therapy. Hyaluronic acid (HA) is a new candidate, which could be applied as a regenerative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan composed of disaccharide repeating elements (N-acetyl-Dglucosamine and D-glucuronic acid). Multiple lines of evidence demonstrated that HA has critical roles in normal tissues. It can be a key player in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of the extracellular matrix. HA has very important physicochemical properties i.e., availability of reactive functional groups and its solubility, which make it a biocompatible material for application in regenerative medicine. Given that HAbased bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic, they are used as soft tissue fillers and injectable dermal fillers. Several studies indicated that HA could be employed as a new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacological effects via affecting stroke-related processes. Herein, we summarized the role of the extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies for the treatment of stroke.