Guided bone regeneration (GBR) is a standard therapy for treating bone defects, with collagen-based barrier membranes widely used clinically. However, these membranes face challenges like early bacterial invasion, risking GBR failure. Effective strategies include orchestrating macrophage activation and controlling their M1 or M2 polarization during bone repair. We present a novel Janus collagen-based barrier membrane with immunomodulatory function. The porous layer promotes direct osteogenic differentiation and inward growth of osteoblasts. The dense layer prevents invasion of soft tissue into bone defects and protects bone defects from bacterial infection. The membrane also enhances rat bone marrow-derived mesenchymal stem cells (rBMSCs) infiltration, proliferation, and osteogenic differentiation by regulating the immune microenvironment. Cranial defect experiments show superior bone regeneration compared to the commercially available Bio-Gide® collagen membrane. Overall, the Janus collagen-based membrane reduces tissue inflammation and fosters an osteoimmune environment conducive to new bone formation, offering innovative material design for advanced GBR technology.