Therapeutic bioengineering based on stem cell therapy holds great promise in biomedical applications. However, the application of this treatment is limited in orthopedics because of their poor survival, weak localization, and low cell retention. In this work, magneto-mechanical bioengineered cells consisting of magnetic silica nanoparticles (MSNPs) and mesenchymal stem cells (MSCs) are prepared to alleviate osteoporosis. The magneto-mechanical bioengineered MSCs with spatial localization, cell retention, and directional tracking capabilities could be mediated by a guided magnetic field (MF) and . Furthermore, high uptake rates of the MSNPs ensure the efficient construction of magnetically controlled MSCs within 2 h. In conjunction with external MF, the magneto-mechanical bioengineered MSCs have the potential for the activation of the YAP/β-catenin signaling pathway, which could further promote osteogenesis, mineralization, and angiogenesis. The synergistic effects of MSNPs and guided MF could also decline bone resorption to rebalance bone metabolism in bone loss diseases. experiments confirm that the functional MSCs and guided MF could effectively alleviate postmenopausal osteoporosis, and the bone mass of the treated osteoporotic bones by using the bioengineered cells for 6 weeks is nearly identical to that of the healthy ones. Our results provide a new avenue for osteoporosis management and treatment, which contribute to the future advancement of magneto-mechanical bioengineering and treatment.