Purpose: The study aimed to investigate the prophylactic value of administering ginger extract versus the combined use of chitosan-coated ginger nanoparticles on tongue wound healing ability in rats exposed to electronic cigarettes (E-cigs) smoke. Methods: 60 rats were randomly assigned into 3 experimental groups as follow: (1) Group I (untreated group), (2) Group II (ginger extract treated group) and (3) Group III (chitosan-coated ginger nanoparticles treated group). All rats were exposed to E-cigs liquid vapor 30 days then tongue incision. At the 7th and 14th days, healing was assessed using histological and immunohistochemical evaluation. Results: This study revealed delayed wound healing in the 7th day in group I and II, however at the 14th day, a thin covering of epithelium was seen. Group III showed marked reduction in inflammation and initial healing at the 7th day. At the 14th day, almost normal epithelium was observed. Positive Ki-67 immunostaining was observed in group III at both periods compared to the other groups. Conclusion: Application of chitosan coated ginger nanoparticles alleviated the effect of E-cigs smoking and enhanced wound healing.