In the recent years, platelet-rich fibrin (PRF) has gained importance in regenerative medicine due to its attributed tissue-inducing properties. However, it is still unclear whether there are benefits from using PRF with open flap debridement (OFD) for the treatment of intrabony defects compared to OFD alone. For this reason, in this study, we performed an overview of systematic reviews with Friendly Summaries of the Body of Evidence using Epistemonikos methodology on the use of PRF with OFD compared to OFD alone for the treatment of intrabony defects. We performed a systematic search in the Epistemonikos database. We extracted data from the included systematic reviews and reanalyzed the data of primary studies and generated a summary of the findings table. We used Review Manager (RevMan) v5.3 software and GRADEpro software for data analysis and data presentation. Eighteen systematic reviews were included after full-text screening, which had 16 clinical trials. Results were reported by the mean difference (MD); the following outcomes were analyzed: change in intrabony defect depth (MD: 1.37 mm more), change in radiographic bone defect filling (MD: 37.26% more), change in probing depth (MD: 1.22 mm more), change in clinical attachment level (MD: 1.32 mm more), and change in gingival margin level (MD: 0.31 more). We concluded that applying PRF with OFD to treat an intrabony defect has some clinical advantages compared to OFD alone.