Aim: The aim of the current study was to prepare a natural oral wound dressing from alginate modified with garden cress (GC), a rich source of antibacterial phytochemical compounds essential for wound healing. Materials and methods: Sodium alginate (SA) dressing (negative control group), was prepared and modified with GC seeds extracts (25 µg/mL and 50 µg/mL) as the intervention groups, and COE-PAK was the positive control group. Cytotoxicity was measured using WST-1 assay (n = 15) after 24 and 48 hours. The in vitro wound healing assay (n = 15) was assessed in terms of wound width, and cell migration rate (0, 24, 48, and 72 hours). Agar diffusion test was performed to investigate the antibacterial action (n = 15) of the groups against Streptococcus mutans and Lactobacillus casei strains. Results were significant at p ≤ 0.05. Results: There was no statistically significant difference in cytotoxicity in all groups (p = 0.24 at 24 hours and 0.1 at 48 hours). Garden cress-containing groups revealed the lowest mean value of wound width (0.27 mm ± 0.01 and 0.23 mm ± 0.01 for 25 µg/mL and 50 µg/mL, respectively at 48 hours) and the highest mean value of cell migration rate (0.013 mm/hour ± 0.004 and 0.014 mm/hour ± 0.004 for 25 µg/mL and 50 µg/mL, respectively at 48 hours), in addition to the highest antibacterial action (1.49 mm ± 0.05 and 2.14 mm ± 0.09 for 25 µg/mL and 50 µg/mL, respectively against S. mutans, 1.43 mm ± 0.07 and 2.55 mm ± 0.09 for 25 µg/mL and 50 µg/mL, respectively against L. casei). Conclusion: Alginate wound dressing modified with GC extract could be considered a promising wound dressing material in terms of wound healing and antibacterial action. Clinical significance: Ready-to-use alginate-based wound dressing modified with GC extract may represent a promising natural alternative to the most commonly used oral wound dressing (COE-PAK).