Successful implant-bone integration remains a formidable challenge in osteoporotic patients, because of excessive inflammatory reactions and osteoclastogenesis around the peri-implant bone tissue. This study designed biomimetic micro/sub-micro hierarchical surfaces on titanium implants based on natural bone hierarchical structures to mitigate macrophage-mediated inflammatory reactions, osteoclastogenesis, and osteogenesis in vitro, as well as promote early osseointegration in vivo. It was found that the biomimetic hierarchical surfaces inhibited M1 macrophage-mediated inflammatory reactions via suppression of the TLR2/NF-κB signaling pathway in vitro. Subsequently, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was observed to be significantly enhanced on hierarchical surfaces in the presence of macrophage conditional media. Furthermore, osteoclast formation was also decreased by inhibiting the osteoclastogenesis regulatory factor NFATc-1 expression on hierarchical surfaces. In vivo, the implant with a micro/sub-micro hierarchical surface underwent rapid and early osseointegration, with the newly formed bone being tightly integrated with the implants. Hence, the hierarchical surface mitigated the inflammatory microenvironment around the implant, thereby inhibiting osteoclastogenesis. This study thus offers a novel biomimetic strategy for designing surface hierarchical topography to facilitate implant-bone osseointegration in osteoporotic patients.