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Aims: To study the role of cytokines and vascular inflammatory biomarkers in unstable carotid plaque. Background: Clinical studies showed that not only the degree of stenosis but also the type of carotid plaque can be responsible for ipsilateral ischemic stroke. Objective: The objective of this study is to suggest a role for vulnerable carotid atherosclerotic disease in the occurrence of ischemic stroke. Methods: PubMed, Embase, Cochrane library, and reference lists have been used to evaluate articles published until February 15, 2021. Results: Several factors may be involved in unstable plaque. Clinical studies support the involvement of brain inflammatory biomarkers as well as cytokines in the unstable carotid plaque. Conclusions: Biomarkers could help to stratify patients with a vulnerable carotid plaque and to personalize the drug treatment. In this review, we briefly discuss the characteristics of vulnerable plaque and the role of biomarkers in the vulnerable carotid plaque.