The aim of this systematic review of randomized controlled trials was to evaluate the adjunctive use of leucocyte- and platelet-rich fibrin (L-PRF) in periodontal endosseous and furcation defects, as compared without L-PRF. The endosseous defect group was subclassified into: L-PRF/open flap debridement (L-PRF/OFD) versus OFD, L-PRF/osseous graft (L-PRF/OG) versus OG, L-PRF/Emdogain (L-PRF/EMD) versus EMD, and L-PRF/guided tissue regeneration (L-PRF/GTR) versus GTR. The furcation defect group was subclassified into L-PRF/OFD versus OFD, and L-PRF/OG versus OG. Mean difference, 95% confidence intervals and forest plots were calculated for probing pocket depth (PPD), clinical attachment level (CAL) and radiographic defect depth (DD). Nineteen studies concerning systemically healthy non-smokers were included. The results of this systematic review and meta-analysis showed in two- and/or three-wall endosseous defects that the adjunctive use of L-PRF to OFD or OG was significantly beneficial for PPD reduction, CAL gain and DD reduction, as compared without L-PRF. Furthermore, the data showed that for two- and/or three-wall endosseous defects, the adjunctive use of L-PRF to GTR was significantly beneficial for CAL and DD improvement, whereas adding L-PRF to EMD had no significant effect, and that for class II furcation defects, the addition of L-PRF to OFD was significantly beneficial for PPD, CAL and DD improvement, whereas the addition of L-PRF to OG was significantly clinically beneficial. In conclusion, this systematic review and meta-analysis found that there was significant clinical and radiographic additive effectiveness of L-PRF to OFD and to OG in two- and/or three-wall periodontal endosseous defects of systemically healthy non-smokers, as compared without L-PRF.