This study aimed to assess the efficacy of biphasic calcium phosphate (BCP) with adjunct recombinant human bone morphogenetic protein-2 (rhBMP-2), with and without collagen membrane (CM), in regeneration of standardized rat calvarial defects. Thirty female Wistar albino rats with a mean age of 12 weeks and mean weight of 300 g were used. The skin over the calvaria was exposed using a full-thickness flap. A standardized defect measuring 4.6 mm in diameter was created in the parietal bone. The defects were randomly divided into the following groups: (1) no treatment (control group); (2) BCP soaked in rhBMP-2 and then covered with a resorbable CM; and (3) BCP soaked in rhBMP-2. Following euthanasia, histologic, histomorphometric, and biomechanical assessments of the calvarial specimens were performed to assess bone regeneration. The results showed islands of newly formed bone (NFB) between the defect edges in the control group. NFB was observed bridging the defect edges and around the remnants of BCP in the rhBMP-2 + BCP + CM group and only around the BCP remnants in the rhBMP-2 + BCP group. Histomorphometric analysis revealed a significantly higher mean ± standard deviation (SD) percentage of NFB per defect in the rhBMP-2 + BCP + CM group (46.12 ± 2.56) compared with the control (11.79 ± 0.75) and rhBMP-2 + BCP (26.65 ± 1.48) groups. Although no differences were found in the hardness and elastic modulus (EM) of NFB between the rhBMP-2 + BCP + CM (hardness: 687.78 ± 4.74 MPa; EM: 27.71 ± 0.063 GPa) and the rhBMP-2 + BCP (hardness: 637.65 ± 6.32 MPa; EM: 21.49 ± 0.095 GPa) groups, the biomechanical parameters of NFB in the control group (hardness: 286.17 ± 9.49 MPa; EM: 12.62 ± 0.048 GPa) were significantly less. The experiment demonstrated the efficiency of rhBMP-2 + BCP in GBR, wherein the presence of CM leads to a greater percentage of new bone formation within standardized calvarial defects.