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Cord blood-platelet lysate (CB-PL), containing growth factors such as a platelet-derived growth factor, has a similar efficacy to peripheral blood-platelet lysate (PB-PL) in initiating cell growth and differentiation, which makes it a unique alternative to be implemented into oral ulceration healing. This research study aimed to compare the effectiveness of CB-PL and PB-PL in promoting oral wound closure in vitro. Alamar blue assay was used to determine the optimal concentration of CB-PL and PB-PL in enhancing the proliferation of human oral mucosal fibroblasts (HOMF). The percentage of wound closure was measured using the wound-healing assay for CB-PL and PB-PL at the optimal concentration of 1.25% and 0.3125%, respectively. The gene expressions of cell phenotypic makers (Col. I, Col. III, elastin and fibronectin) were determined via qRT-PCR. The concentrations of PDGF-BB were quantified using ELISA. We found that CB-PL was as effective as PB-PL in promoting wound-healing and both PL were more effective compared to the control (CTRL) group in accelerating the cell migration in the wound-healing assay. The gene expressions of Col. III and fibronectin were significantly higher in PB-PL compared to CB-PL. The PDGF-BB concentration of PB-PL was the highest and it decreased after the wound closed on day 3. Therefore, we concluded that PL from both sources can be a beneficial treatment for wound-healing, but PB-PL showed the most promising wound-healing properties in this study.