OBJECTIVE To investigate the gene expression profile of human gingiva following surgical wounding. METHODS Ten volunteers had one side of the palate wounded. Five days later, biopsies were harvested from both wounded (healing gingiva) and contra-lateral site (normal gingiva). Tissue samples were processed for gene expression (RNA-Seq, real-time PCR) and immunohistochemistry. Gene set enrichment/pathway analysis was also performed. RESULTS Seven hundred genes were significantly differentially expressed in healing gingiva. Among genes with >twofold change (FC) in expression, 399 genes were up-regulated and 88 down-regulated, several not previously reported expressed in gingiva. Most increased in expression (≥30-FC) were MMP1, CCL18, SPP1, MUC21, CTHRC1, MMP10, and SERPINE1; most decreased (≥7-FC) were COCH, SIAH3, MT4, IGFL3, KY, and SYT16. Real-time PCR confirmed significantly changed mRNA levels for selective genes tested. Gene set enrichment analysis revealed several significantly enriched biological pathways. Immunohistochemistry confirmed protein expression of MUC21, CTHRC1, CTGF, and SYT16 in normal and healing gingiva. CONCLUSIONS This first comprehensive analysis of the human gingival transcriptome during surgical wound healing offers novel insights into the participating molecular and biological mechanisms. The present results could serve as basis for future investigations into gingival wound healing following surgical, traumatic, or other type of injury.