Objectives <p>This study aimed to compare the effects of locally applied hyaluronic acid (HA) and injectable platelet-rich fibrin (I-PRF) on patient morbidity, oral health-related quality of life (OHRQoL), and healing of palatal donor sites, palatal tissue consistency, complete epithelization (CE), and color match (CM).</p> Materials and methods <p>Sixty-seven patients undergoing free gingival grafting (FGG) were randomly assigned to three groups in an examiner-masked clinical trial. Test group 1 received a 0.8% HA gel-impregnated gelatin sponge, test group 2 received an I-PRF-impregnated sponge, and the control group received a sterile sponge. Pain and burning were assessed via a visual analog scale (VAS) on days 3, 7, 14, and 21. CM was evaluated on days 3, 7, 14, 21, 28, and at months 1 and 3. CE and Landry Wound Healing Index (WHI) were recorded on days 3, 7, 14, 21, and 28.</p> Results <p>Topical application of hyaluronic acid (HA) and injectable platelet-rich fibrin (I-PRF) significantly reduced postoperative discomfort and improved complete epithelization (CE) compared to the control group (<i>p</i> &lt; 0.05). HA showed better outcomes than I-PRF in wound healing and morbidity, while I-PRF also significantly reduced postoperative pain (<i>p</i> &lt; 0.05). Palatal tissue thickness at the 1st and 3rd months differed significantly among groups (<i>p</i> = 0.001), and OHRQoL scores decreased significantly from day 7 to day 14 in all groups (<i>p</i> &lt; 0.05).</p> Conclusion <p>The adjunctive use of HA or I-PRF with gelatin sponge is more effective in minimizing discomfort and enhancing healing at palatal donor sites than sponge use alone.</p> Clinical relevance <p>Optimizing healing and minimizing patient discomfort at palatal donor sites are crucial for improving outcomes in free gingival grafting procedures. This study demonstrates that the adjunctive application of HA or I-PRF significantly enhances soft tissue healing and reduces postoperative morbidity. Particularly, HA was found to be more effective in promoting wound healing and comfort. These findings support the clinical use of HA or I-PRF as simple, biocompatible adjuncts to improve patient experience and surgical outcomes in periodontal procedures.</p> Clinical trial number <p>NCT06867055<a href="https://www.ClinicalTrials.gov">https://www.ClinicalTrials.gov</a>&#xa0;03/04/2025‘Retrospectively registered.</p>