This dataset contains data-independent acquisition (DIA) LC–MS/MS proteomic profiles of human mandible tissues obtained from patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) and healthy controls. Frozen tissues were processed using phenol–methanol extraction, SP3-based cleanup, and tryptic digestion, followed by high-resolution LC–MS/MS in DIA mode. Protein identification and quantification were performed under a 1% FDR cutoff with intensity-based normalization. Comparative analysis revealed key alterations in BRONJ samples.