Peripheral giant cell granuloma (PGCG) is a non-neoplastic, tumour-like reactive lesion that exclusively involves the gingiva and/or the alveolar crest. The surgical approach with a scalpel has been the golden standard of treatment for PGCG, but the scientific literature reports a high rate of lesion recurrence. Hence, this unique case report aimed to evaluate the efficacy of λ 10,600 nm high-level laser therapy (HLLT) in eradicating persistent, aggressive, and recurrent PGCG that failed to respond to standard surgical treatment. A fit and healthy thirty-four-year-old Caucasian male presented with a two-month history of recurrent episodes of an oral mucosal lesion involving the buccal and lingual interdental papillae between the lower right second premolar (LR5) and lower right first molar (LR6), which was surgically excised with a scalpel three times previously. A λ 10,600 nm-induced HLLT was chosen as a treatment modality at a lower peak power of 1.62 W, measured with a power metre, emitted in gated emission mode (50% duty cycle), whereby the average output power reaching the target tissue was 0.81 W. The spot size was 0.8 mm. Ninety seconds was the total treatment duration, and the total energy density was 7934.78 J/cm2. Patient self-reporting outcomes revealed minimal to no post-operative complications. Initial healing was observed on the 4th day of the post-laser treatment, and a complete healing occurred at two-weeks post-operatively. The histological analysis revealed PGCG. This unique case report study demonstrated the efficacy of λ 10,600 nm-induced HLLT and its superiority to eradicate persistent aggressive PGCG over the standard surgical approach with minimal to no post-operative complications, accelerating wound healing beyond the physiological healing time associated with no evidence of PGCG recurrence at the six-month follow-up timepoint. Based on the significant findings of this unique study and the results of our previous clinical studies, we can confirm the validity and effectiveness of our standardised λ 10,600 nm laser dosimetry-induced HLLT and treatment protocol in achieving optimal outcomes. Randomised controlled clinical trials with large data comparing λ 10,600 nm with our dosimetry protocol to the standard surgical treatment modality at long follow-up timepoints are warranted.