Lithiated porous silicon nanowires (LipSiNs) stimulate periodontal regeneration by combining lithium and silicic acid release. This study introduces a method to lithiate porous silicon nanowires, generating a biocompatible and bioresorbable material. LipSiNs incorporate lithium between 1% and 40% of silicon content, releasing lithium and silicic acid in a controllable manner over days to weeks. LipSiNs provide osteogenic, cementogenic, and Wnt/β-catenin stimuli, promoting regeneration of bone, cementum, and periodontal ligament fibers in mice. Periodontal disease is a major oral health issue, affecting 19% of the global adult population. The periodontium, a complex structure supporting the tooth, is challenging to regenerate due to its mix of mineralized and soft tissues. Silicon-based materials are osteoinductive and play a key role in mineralized tissue regeneration. Incorporating lithium into silicon-based materials enhances their regenerative capacity by inhibiting GSK3 and activating the Wnt/β-catenin pathway, which is crucial for osteogenesis and tissue regeneration. Bioactive glasses and aluminosilicate clays containing lithium can provide sustained release of lithium and silicate ions, but their regenerative efficacy is limited by material formulation and release kinetics. Porous silicon offers a promising alternative for controlled ion release, with tunable particle size and bioresorption. Lithiation of porous silicon nanowires allows for precise control over lithium incorporation, enabling tailored release profiles. The study demonstrates that LipSiNs, when exposed to phosphate buffer, release lithium and silicate ions, with release kinetics modulated by lithiation conditions. LipSiNs show improved biocompatibility and bioactivity compared to unmodified porous silicon nanowires. In vitro tests show that LipSiNs stimulate Wnt/β-catenin signaling and osteogenesis in human periodontal ligament stem cells. In vivo tests in mouse models show that LipSiNs stimulate Wnt/β-catenin signaling and promote bone regeneration in periodontal defects. In a rat model of periodontal fenestration defect, LipSiNs improved bone mineral density and volume compared to control groups. Histological analysis confirmed bone, cementum, and periodontal ligament regeneration. LipSiNs also showed comparable effectiveness to lithium-substituted bioglass in promoting bone regeneration. The study highlights the potential of LipSiNs for periodontal regeneration and other biomedical applications requiring sustained lithium release.Lithiated porous silicon nanowires (LipSiNs) stimulate periodontal regeneration by combining lithium and silicic acid release. This study introduces a method to lithiate porous silicon nanowires, generating a biocompatible and bioresorbable material. LipSiNs incorporate lithium between 1% and 40% of silicon content, releasing lithium and silicic acid in a controllable manner over days to weeks. LipSiNs provide osteogenic, cementogenic, and Wnt/β-catenin stimuli, promoting regeneration of bone, cementum, and periodontal ligament fibers in mice. Periodontal disease is a major oral health issue, affecting 19% of the global adult population. The periodontium, a complex structure supporting the tooth, is challenging to regenerate due to its mix of mineralized and soft tissues. Silicon-based materials are osteoinductive and play a key role in mineralized tissue regeneration. Incorporating lithium into silicon-based materials enhances their regenerative capacity by inhibiting GSK3 and activating the Wnt/β-catenin pathway, which is crucial for osteogenesis and tissue regeneration. Bioactive glasses and aluminosilicate clays containing lithium can provide sustained release of lithium and silicate ions, but their regenerative efficacy is limited by material formulation and release kinetics. Porous silicon offers a promising alternative for controlled ion release, with tunable particle size and bioresorption. Lithiation of porous silicon nanowires allows for precise control over lithium incorporation, enabling tailored release profiles. The study demonstrates that LipSiNs, when exposed to phosphate buffer, release lithium and silicate ions, with release kinetics modulated by lithiation conditions. LipSiNs show improved biocompatibility and bioactivity compared to unmodified porous silicon nanowires. In vitro tests show that LipSiNs stimulate Wnt/β-catenin signaling and osteogenesis in human periodontal ligament stem cells. In vivo tests in mouse models show that LipSiNs stimulate Wnt/β-catenin signaling and promote bone regeneration in periodontal defects. In a rat model of periodontal fenestration defect, LipSiNs improved bone mineral density and volume compared to control groups. Histological analysis confirmed bone, cementum, and periodontal ligament regeneration. LipSiNs also showed comparable effectiveness to lithium-substituted bioglass in promoting bone regeneration. The study highlights the potential of LipSiNs for periodontal regeneration and other biomedical applications requiring sustained lithium release.