Premalignant lesions like oral lichen planus (OLP), oral leukoplakia (OL) has a fair probability of transforming into malignancy and they are perverse toward conventional therapies. Photodynamic therapy (PDT) has been considered as an alternative/complimentary therapeutic modality for the management of premalignant lesions. In this study, methylene blue-mediated photodynamic therapy (MB-PDT) was used as a possible alternative method for the treatment of OLP and OL. A total of 15 OLP lesions and 13 OL lesions were enrolled in the study. The patients were irradiated using metal halide lamp filtered at 630 ± 10 nm, with a light exposure dose of 120 J/cm2 per sitting. For the OLP lesions, MB-PDT was performed once a week for four weeks and for the OL lesions, MB-PDT was performed twice a week for three weeks. Lesions were evaluated pre- and post- and at follow-up sessions by changes in sign and symptom scores, and size of lesions. We have observed a 53.3% of complete reduction in the treated OLP lesions and their decrease in size, sign and symptom score after treatment and at follow-up session was statistically significant. We have also observed complete response for one OL lesion of the 13 treated lesions. The result indicates that MB-PDT is an effective modality in management of OLP and OL. Among the two types of premalignancies treated with MB-PDT, OLP lesions responded much better than that of OL.