Cancer treatment with chemotherapy or radiotherapy is associated with some side effects including in the oral cavity. One of the more significant oral complications is oral mucositis (OM) which induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking. Although advancements in cancer treatment improved the survival rate, severe OM and opportunistic infection affect treatment adversely. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and photodynamic therapy (PT) are noninvasive methods that reduce inflammation and pain during wound healing. The aim of this study is to evaluate immunohistochemical and histological examination of the OM region of the PT comparing LLLT. In this study, 24 Sprague-Dawley rats were divided into three groups as control, LLLT, and PT groups. All groups received 5-fluorouracil intraperitoneally and a linear trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the LLLT group was administered LLLT, and the PT group had LLLT after indocyanine green application. Then all groups were sacrificed, and histological analyses and protein level detection of basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), and platelet-derived growth factor (PDGF-BB) were evaluated in all groups. PT was determined to be more statistically significantly than LLLT with bFGF and PDGF-BB. However, regarding TGF-beta, no statistically significant difference was observed between the groups. Within the limitations of this study, indocyanine green may accelerate the LLLT effect. However, further studies on this subject are required.