A present, photobiomodulation therapy (PBMT) effectiveness in enhancing bone regeneration in bone defects grafted with or without biomaterials is unclear. This systematic review (PROSPERO, ref. CRD 42019148959) aimed to critically appraise animal in vivo published data and present the efficacy of PBMT and its potential synergistic effects on grafted bone defects. MEDLINE, CCCT, Scopus, Science Direct, Google Scholar, EMBASE, EBSCO were searched, utilizing the following keywords: bone repair; low-level laser therapy; LLLT; light emitting diode; LEDs; photobiomodulation therapy; in vivo animal studies, bone substitutes, to identify studies between 1994 and 2019. After applying the eligibility criteria, 38 papers included where the results reported according to "PRISMA." The results revealed insufficient and incomplete PBM parameters, however, the outcomes with or without biomaterials have positive effects on bone healing. In conclusion, in vivo animal studies with a standardized protocol to elucidate the effects of PBMT on biomaterials are required initially prior to clinical studies.