Oral potential malignant disorders (OPMDs) have a high risk of malignant transformation and recurrence. This case reports describes a novel therapeutic strategy of Er:YAG laser-assisted photodynamic therapy (Er:YAG-PDT) combined with anti-programmed death protein-1 (anti-PD-1) immunotherapy for a patient with refractory OPMDs in the right lower gingiva following oral squamous cell carcinoma (OSCC) surgery on the contralateral side. Initial PDT alone showed limited efficacy, but after integrating Er:YAG laser pretreatment, the patient achieved significant lesion regression, with a complete final clearance. The 6-month follow-up showed good local lesion control in the patient peripheral blood analysis revealed elevated natural killer (NK) cell level and reduced regulatory T (Treg) cell percentage, suggesting activated adaptive immunity, while similar CD8⁺ T cell levels indicated maintained immune homeostasis. This case report highlights the potential of combined Er:YAG-PDT and anti-PD-1 therapy for OPMDs, while emphasizing the need for optimized monitoring and multi-modal strategies to prevent recurrence in high-risk patients.