BackgroundAn altered blood lipid profile has been considered as a diagnostic and/or prognostic marker for cancer. Since oral cancer is usually preceded by oral potentially malignant disorders (OPMDs) and share common etiopathogenesis, thus researchers have tried to explore the role of blood lipid profile as a marker for OPMDs; however, no consensus has been made regarding the utilization of serum lipid profile as a biomarker for oral submucous fibrosis (OSMF). Thus, the present article aimed to validate serum lipid profile as a biomarker for OSMF.MethodologyPubMed, Scopus, Google Scholar and Clinical key databases were searched for relevant articles. Thirty‐six studies that met the eligibility criteria were included for qualitative review, however, out of these, 27 studies with specific data for OSMF and the control group were included in the meta‐analysis.ResultsA significant reduction in very low‐density lipoprotein (p = 0.042), low density lipoprotein (p = 0.006), high density lipoprotein (p = 0.020), triglyceride (p = 0.049) and total cholesterol (p = 0.009) levels in blood were observed in OSMF patients in comparison to healthy controls whereas no significant difference was seen in contrast to oral squamous cell carcinoma patients.ConclusionAlthough a significant alteration was observed in lipid levels in OSMF patients, considerable heterogeneity in all the studied parameters implies that blood lipid profile could not be used as a reliable biomarker for OSMF and require further investigation.