Background: Although hyaluronic acid (HA) has long been used for many medical applications, only in recent years has it gained greater popularity in the field of periodontics because of its biological effects during wound healing. Even today, most clinicians are not aware that more than one type of HA exists and that the extent of its biological functions may vary depending upon the particular characteristics of the biomolecule itself. Aim: To review and synthesize the current preclinical and clinical evidence on the biological effects and therapeutic applications of HA in periodontology, with a focus on its role in wound healing and regeneration. Materials and methods: The origin and chemical structure of HA are discussed first, with a focus on the importance of its molecular weight and the possibility of modifying its structure and form. The main biological properties of HA followed by its effects on the cells of periodontal tissues are summarized and followed by the presentation of the results from preclinical studies in animals which have evaluated the effects of HA in various types of defects. Subsequently, the data from clinical studies evaluating the application of HA in nonsurgical periodontal therapy, regenerative periodontal surgery, and mucogingival surgery are summarized, and recommendations for the clinicians are provided. Results: The preclinical and clinical evidence indicates that HA accelerates the wound healing process through inflammatory mechanisms and enhances blood clot stability when applied to the root surface. It also influences the expression of both mineralized tissue markers and cementoblast-specific genes, suggesting a potential role in cementum regeneration. HA strongly promotes osteoprogenitor growth while maintaining stemness, potentially regulating the balance between self-renewal and differentiation during bone regeneration. Additionally, HA enhances periodontal ligament (PDL) cell adhesion and proliferation. It has been shown to improve the proliferative and migratory abilities of cells while inducing the expression of collagen type III alpha 1 (COL3A1) and TGFβ-3 genes, which are characteristic of scarless fetal wound healing. Certain HA formulations upregulate the expression of genes encoding platelet-derived growth factor B (PDGFB), fibroblast growth factor 2 (FGF-2), and epidermal growth factor (EGF), all of which play crucial roles in the healing process. Histologic evidence from animal studies suggests that HA may promote periodontal regeneration when applied both non-surgically and surgically—particularly in intrabony defects, gingival recessions, and, to some extent, in furcation defects. The data from clinical studies revealed that HA leads to statistically significant and clinically relevant improvements of probing depths and clinical attachment levels when used in conjunction with nonsurgical periodontal therapy and surgical therapy in intrabony and recession defects. Conclusion: The available data from preclinical and clinical studies provide robust evidence on the effects of HA to enhance periodontal wound healing and regeneration, and on the improved clinical outcomes when HA is used in conjunction with nonsurgical periodontal therapy and regenerative surgery in intrabony and recession defects.