Quercetin (Que), a natural flavonoid, has shown potential in the prevention and treatment of osteoporosis (OP). This review summarizes the pharmacological and mechanistic aspects of Que in OP, highlighting its effects on bone formation and resorption. Que promotes osteoblast (OB) differentiation and activity while inhibiting osteoclast (OC) differentiation and activity through various pathways, including Wnt/β-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. It enhances bone formation by increasing osteoblast differentiation, matrix mineralization, and the expression of bone-related proteins such as osteocalcin and osteopontin. Conversely, Que inhibits OC-mediated bone resorption by regulating transcription factors, inflammatory factors, and the OPG/RANKL/RANK signaling pathway. Additionally, Que exhibits anti-inflammatory and antioxidant properties, which contribute to its protective effects against bone loss. Que is primarily found in plants, including onions, apples, berries, and broccoli, and is available in various forms, such as glycosides. Its physicochemical properties include solubility in cold ethanol, hot ethanol, methanol, and other solvents, but it is not soluble in water. The biosynthesis of Que involves the phenylpropyl metabolic pathway, starting from phenylalanine and involving several enzymatic steps. Pharmacokinetic studies show that Que is rapidly metabolized in the blood and has a short half-life. Major metabolites include Que-30-sulfate, Que-3-glucuronide, and Que-3-sulfate. The in vitro bioavailability of Que is low, but various delivery systems have been developed to enhance its solubility and bioavailability. Toxicological studies indicate that Que is generally safe, with no significant adverse effects observed in chronic toxicity studies. However, some concerns about its potential carcinogenicity remain, though no conclusive evidence has been found. Future research should focus on improving the bioavailability of Que through chemical modifications and composite carriers, as well as exploring its interactions with other compounds and its role in bone metabolism through the regulation of intestinal flora. Clinical and in vivo studies are needed to further validate the therapeutic potential of Que in the treatment of OP and other diseases. Overall, Que shows promise as a potential drug for the prevention and treatment of osteoporosis.Quercetin (Que), a natural flavonoid, has shown potential in the prevention and treatment of osteoporosis (OP). This review summarizes the pharmacological and mechanistic aspects of Que in OP, highlighting its effects on bone formation and resorption. Que promotes osteoblast (OB) differentiation and activity while inhibiting osteoclast (OC) differentiation and activity through various pathways, including Wnt/β-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. It enhances bone formation by increasing osteoblast differentiation, matrix mineralization, and the expression of bone-related proteins such as osteocalcin and osteopontin. Conversely, Que inhibits OC-mediated bone resorption by regulating transcription factors, inflammatory factors, and the OPG/RANKL/RANK signaling pathway. Additionally, Que exhibits anti-inflammatory and antioxidant properties, which contribute to its protective effects against bone loss. Que is primarily found in plants, including onions, apples, berries, and broccoli, and is available in various forms, such as glycosides. Its physicochemical properties include solubility in cold ethanol, hot ethanol, methanol, and other solvents, but it is not soluble in water. The biosynthesis of Que involves the phenylpropyl metabolic pathway, starting from phenylalanine and involving several enzymatic steps. Pharmacokinetic studies show that Que is rapidly metabolized in the blood and has a short half-life. Major metabolites include Que-30-sulfate, Que-3-glucuronide, and Que-3-sulfate. The in vitro bioavailability of Que is low, but various delivery systems have been developed to enhance its solubility and bioavailability. Toxicological studies indicate that Que is generally safe, with no significant adverse effects observed in chronic toxicity studies. However, some concerns about its potential carcinogenicity remain, though no conclusive evidence has been found. Future research should focus on improving the bioavailability of Que through chemical modifications and composite carriers, as well as exploring its interactions with other compounds and its role in bone metabolism through the regulation of intestinal flora. Clinical and in vivo studies are needed to further validate the therapeutic potential of Que in the treatment of OP and other diseases. Overall, Que shows promise as a potential drug for the prevention and treatment of osteoporosis.