In recent decades, the potential of PRF has been extensively studied. The number of studies about PRF has increased three times since the year 2012, but the full spectrum of its fundamental properties, such as antimicrobial and anti-inflammatory activity, is not clearly described. In oral and maxillofacial surgery, PRF is described in alveolar ridge preservation, orthognathic surgery, cleft lip and palate surgery, maxillary sinus augmentation, and dental implant placement as demonstrating favorable results and its clinical advantages. The structural complexity, inhomogeneous nature, and clotting ability of PRF make its antimicrobial effect evaluation complicated. Nevertheless, most of the used antimicrobial testing methods are based on antibacterial agent diffusion ability in culture media. Because the oral and maxillofacial region is the most frequent area of PRF application, its antimicrobial activity evaluation also prevails in the oral microbiome. PRF’s biological potential is highly dependent on the specific preparation protocol and methodology used; it should be carefully prepared and kept under proper conditions to keep cellular content alive. PRF’s influence on living cells demonstrates a stimulating effect on bone regeneration, and an angiogenetic effect, and it provides anti-inflammatory activity. According to analyzed studies, PRF demonstrated success in oral and maxillofacial surgery in various methods of application. Antibacterial and anti-inflammatory properties were proven by antibacterial activity against different bacterial species, sustained growth factor, sustained release, and cell activity on the material application. Accurately and correctly prepared PRF can ensure antibacterial and anti-inflammatory properties, and it can be a beneficial clinical tool in oral and maxillofacial surgery.