Fractional laser photothermolysis, long established in dermatology, enables controlled microthermal injury that stimulates repair without scarring, but its potential in oral tissue regeneration has not been systematically explored. In this study, we conducted the first controlled experimental evaluation of a 1550 nm erbium fiber laser for oral mucosa regeneration. Thirty-two rabbits underwent fractional photothermolysis at energy levels of 70, 100 and 130 kJ, with gingival biopsies collected at 1, 14, 28 and 42 days for histological and immunohistochemical assessment of epithelial repair, stromal remodeling, inflammation and angiogenesis. All energy modes produced microcoagulation columns followed by progressive epithelial thickening, fibroblast proliferation and neoangiogenesis. The 70 kJ mode occasionally led to residual fibrosis, whereas higher energies (100–130 kJ) promoted effective connective tissue remodeling and de novo tissue formation without scarring. Complete epithelial recovery occurred within two weeks, indicating a safe and optimal interval for repeated exposure. Overall, the results demonstrate that 1550 nm fractional photothermolysis is a safe and effective method to induce regenerative responses in oral tissues, establishing a foundation for its translational application in periodontal and peri-implant regeneration. © 2025 by the authors.