This review article explores the pharmacological and mechanistic aspects of quercetin (Que) in the context of osteoporosis (OP). OP is a common bone disease characterized by decreased bone mass and increased fracture risk, affecting over 200 million people worldwide. Traditional treatments, such as anabolic agents and anti-resorptive agents, often have adverse effects and are not suitable for long-term use. Quercetin, a widely available flavonoid, has shown promise as a potential therapeutic agent for OP due to its osteoprotective properties. The review highlights the biological, pharmacological, pharmacokinetic, and toxicological properties of Que. It demonstrates that Que enhances bone formation by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity through various pathways, including Wnt/β-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Additionally, Que promotes bone matrix formation and mineralization by upregulating the expression of bone-related proteins such as bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN). Inhibiting osteoclast-mediated bone resorption, Que regulates transcription factors, inflammatory factors, the OPG/RANKL/RANK signaling pathway, and the ERK1/2/JNK signaling pathway. The review also discusses the combination of Que with other phytochemicals, which has shown synergistic anti-osteoporotic effects. Pharmacokinetic studies reveal that Que is rapidly metabolized in the blood with a short half-life. Its low solubility and bioavailability are limitations, but these can be improved through chemical modifications and composite carriers. Toxicological studies indicate that Que is generally considered safe, with some reports of potential genotoxicity and chronic kidney disease. The authors conclude that Que is a promising novel drug for the prevention and treatment of OP, with further research needed to optimize its dosage and application in clinical settings.This review article explores the pharmacological and mechanistic aspects of quercetin (Que) in the context of osteoporosis (OP). OP is a common bone disease characterized by decreased bone mass and increased fracture risk, affecting over 200 million people worldwide. Traditional treatments, such as anabolic agents and anti-resorptive agents, often have adverse effects and are not suitable for long-term use. Quercetin, a widely available flavonoid, has shown promise as a potential therapeutic agent for OP due to its osteoprotective properties. The review highlights the biological, pharmacological, pharmacokinetic, and toxicological properties of Que. It demonstrates that Que enhances bone formation by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity through various pathways, including Wnt/β-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Additionally, Que promotes bone matrix formation and mineralization by upregulating the expression of bone-related proteins such as bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN). Inhibiting osteoclast-mediated bone resorption, Que regulates transcription factors, inflammatory factors, the OPG/RANKL/RANK signaling pathway, and the ERK1/2/JNK signaling pathway. The review also discusses the combination of Que with other phytochemicals, which has shown synergistic anti-osteoporotic effects. Pharmacokinetic studies reveal that Que is rapidly metabolized in the blood with a short half-life. Its low solubility and bioavailability are limitations, but these can be improved through chemical modifications and composite carriers. Toxicological studies indicate that Que is generally considered safe, with some reports of potential genotoxicity and chronic kidney disease. The authors conclude that Que is a promising novel drug for the prevention and treatment of OP, with further research needed to optimize its dosage and application in clinical settings.