Background Oral potential malignant disorders (OPMDs) are lesions and conditions that increase the risk for malignant transformation. OPMDs have an impact on patients’ health status and Quality of life (QoL). The aim of our study is to evaluate and compare QoL in patients with oral lichen planus and oral epithelial dysplasia as a setting of clinical leukoplakia. Methods This is a cross-sectional study with a sample size of 100 patients divided into, 53 subjects with Oral Lichen Planus (53.0%), 39 patients with oral epithelial dysplasia as a setting of solitary leukoplakia (39.0%), and 8 subjects with oral lichen planus with oral epithelial dysplasia (8.0%). Patients who fit the criteria were asked to fill out three different questionnaires. 26-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-26), Hospital Anxiety and Depression Scale (HADS), and the Oral potentially malignant disorders QoL questionnaire (OPMDsQoL). Results Both the COMD-26 and OPMDQoL questionnaire scores were significantly different across the three disease groups. Relative to patients aged >65, the 40-64 age group added 6.8 points to the COMD-26 survey score (P < 0.05). Relative to oral epithelial dysplasia, oral lichen planus added 15.7 points to the COMD-26 survey score (P < 0.001). Relative to oral epithelial dysplasia, oral lichen plus added 8.9 points to the OPMDQoL survey score (P = 0.003). Conclusion Within the limitation of our study OLP shows significant poorer QoL in compared to OED as a setting of clinical OL. Younger individuals affected with OLP, and OED showed significant impact in QoL in compared to older individuals.