Background:Prevalence and incidence of oral mucositis (OM) are rigorously increasing and there is no effective treatment. The herbal formulation “HTOR-091516” containing Curcuma longa, Triphala and honey were evaluated for the treatment of OM.Aim:The aim of this study was to evaluate the safety and efficacy of HTOR-091516, employing cellular model, human gingival fibroblasts-1 (HGF-1), and 5-fluorouracil (5-FU)-induced mucositis model in rats.Materials and Methods:The cell viability was assessed using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay and the inhibitory effect of HTOR-091516 on tumor necrosis factor-alpha (TNF-α) was evaluated using TNF-α bioassay in lipopolysaccharides-induced HGF-1. 5-FU and glacial acetic acid were used to induce OM in rats. Animals were divided into two groups, group 1 served as mucositis control and group 2 was treated with HTOR-091516 at the dose of 200 μl and TNF-α was estimated in plasma samples.Results:The in vitro safety of HTOR-091516 was evaluated in reconstructed human oral epidermis and was found to be nontoxic and exhibited concentration-dependent TNF-α inhibition in HGF-1. The treatment with HTOR-091516 reduced mucositis scores and mortality rate and also decreased the plasma TNF-α level.Conclusion:The present data indicate that HTOR-091516 is effective in the treatment of OM.