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