Oral mucositis is a common complication of intensive cancer chemotherapy and radiotherapy. Generally, the treatment options for this condition are largely palliative and no adequate treatment with conclusive evidence till now exists. Olive leaf extract is a natural product exerts antimicrobial, anti-inflammatory and anti-oxidant activities. The present project aimed to evaluate the potential effect of olive leaf extract as a local treatment for chemotherapy induced mucositis. The role of oral flora in developing oral mucositis was also assessed. Therefore, olive leaf extract was investigated thoroughly through microbiological, experimental animal studies and clinical trial. The results were compared with the action of benzydamine HCl as positive control and normal saline as negative control. This project showed that both olive leaf and benzydamine HCl were effective in reducing the incidence and decreasing the severity of oral mucositis and exert wide range of antimicrobial activity against pre isolated oral microorganisms. Accordingly we suggest using this medication for oral mucositis as a safe (herbal) and effective treatment modality.