Hyaluronic acid (HA) is widely used in aesthetic medicine for its moisturizing and anti-aging action. This molecule, which is naturally present in the body, has an interesting response to aging, accentuated in totally edentulous patients. While its aesthetic benefits for facial rejuvenation are well-documented, there is a lack of description and investigation on its therapeutic usefulness for edentulous patients. The management of completely edentulous patients is a daily reality in dental practice and requires specific attention. The aesthetic and functional challenge is considerable. The displacement of the bone base, which is often marked, and lack of soft tissue support are sometimes difficult to correct with prosthetic reconstruction. This review aims to present the physiological processes appearing in completely edentulous patients and prosthetic solutions available to recreate oral functions and counteract facial aging. As prosthetic rehabilitations are not fully satisfying for counterbalancing the impression of excessive facial aging, we investigated the applications of HA injection in the perioral area, in order to improve edentulism treatment, and discussed the advantages and disadvantages, compared to other dermal fillers and rejuvenation therapies. Considering the specific situations of edentulous patients, dermal HA injections help to correct uncompensated bone losses and mucous volume losses and appear to be a therapeutically beneficial for treating completely edentulous patients, without the requirement to full rejuvenation therapy.