Background: Topical applications have long been regarded as precise methods for delivering drugs to soft tissues, such as the periodontal ligament, as well as hard structures, including the alveolar bone and cementum. Recently, the combination of hyaluronic acid (HA) and ozone therapy has gained popularity as a supportive treatment for chronic inflammation, in addition to its established role in enhancing healing after dental procedures. Methods: To gather the necessary research for our study, we conducted a systematic search across several databases, including PubMed, Google Scholar, and Ovid. Our study was registered under Prospero number CRD42024569641. The research, which began in June 2015 and concluded in May 2024, systematically examined the potential benefits of topical HA application in the management of both acute and chronic inflammatory diseases. Using relevant keywords and Medical Subject Headings, we selected 28 pertinent studies: three related to gingivitis, thirteen on chronic periodontitis, seven involving dental surgeries such as implants and sinus lifts, and three on oral ulcers. Results: The risk of bias among the analyzed studies was assessed using the RoB 2 tool. Regarding the randomization process, 75% of the studies exhibited a high risk of bias. However, all studies (100%) had a low risk of bias concerning allocation concealment. Only 25% of the studies adequately addressed performance bias, and another 25% reported all outcome data. Nevertheless, 85% of the included studies showed a low risk of reporting bias. Conclusions: The results indicate that the use of topical HA in combination with ozone therapy is highly effective not only in promoting post-operative healing following dental procedures but also in providing positive outcomes for individuals dealing with chronic gingivitis, periodontal inflammation, and oral ulcers.