IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism. This study shows that glutamine (Glu) is essential for osteoclast differentiation and function. Glu deprivation or pharmacological inhibition of the Glu transporter ASCT2 by V9302 suppresses osteoclast differentiation and bone resorption. In vivo treatment with V9302 improves osteoporosis-induced bone loss. Mechanistically, RNA-seq and in vitro/in vivo experiments reveal that Glu mediates the role of IL-17 in promoting osteoclast differentiation and regulating energy metabolism. In vivo IL-17 treatment exacerbates osteoporosis-induced bone loss, which requires Glu or its downstream metabolite α-KG. This study reveals that IL-17 regulates energy metabolism in a Glu-dependent manner. Targeting the IL-17-Glu-energy metabolism axis may be a potential therapeutic strategy for osteoporosis and other IL-17-related diseases. Osteoclasts consume ATP to perform bone resorption, and their energy metabolism is regulated by Glu. Glu is transported into cells by ASCT2 and converted to α-KG, which enters the TCA cycle. Glu deficiency reduces α-KG formation and impairs osteoclast energy metabolism. α-KG supplementation rescues this effect. IL-17 promotes osteoclast differentiation by increasing energy production, but this effect is inhibited by Glu deprivation or pharmacological block of Glu transport. In vivo, IL-17 exacerbates osteoporosis-induced bone loss, which is suppressed by V9302. α-KG supplementation partially rescues the effects of V9302 on bone mass. These results indicate that IL-17 promotes osteoclast formation and accelerates bone loss in vivo, which requires the participation of Glu. This study reveals a previously unrecognized IL-17-Glu-energy metabolism axis, which is important for osteoclast differentiation and contributes to osteoclast-mediated bone loss. Targeting this axis may be a novel therapeutic strategy for osteoporosis and other IL-17-related diseases.IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism. This study shows that glutamine (Glu) is essential for osteoclast differentiation and function. Glu deprivation or pharmacological inhibition of the Glu transporter ASCT2 by V9302 suppresses osteoclast differentiation and bone resorption. In vivo treatment with V9302 improves osteoporosis-induced bone loss. Mechanistically, RNA-seq and in vitro/in vivo experiments reveal that Glu mediates the role of IL-17 in promoting osteoclast differentiation and regulating energy metabolism. In vivo IL-17 treatment exacerbates osteoporosis-induced bone loss, which requires Glu or its downstream metabolite α-KG. This study reveals that IL-17 regulates energy metabolism in a Glu-dependent manner. Targeting the IL-17-Glu-energy metabolism axis may be a potential therapeutic strategy for osteoporosis and other IL-17-related diseases. Osteoclasts consume ATP to perform bone resorption, and their energy metabolism is regulated by Glu. Glu is transported into cells by ASCT2 and converted to α-KG, which enters the TCA cycle. Glu deficiency reduces α-KG formation and impairs osteoclast energy metabolism. α-KG supplementation rescues this effect. IL-17 promotes osteoclast differentiation by increasing energy production, but this effect is inhibited by Glu deprivation or pharmacological block of Glu transport. In vivo, IL-17 exacerbates osteoporosis-induced bone loss, which is suppressed by V9302. α-KG supplementation partially rescues the effects of V9302 on bone mass. These results indicate that IL-17 promotes osteoclast formation and accelerates bone loss in vivo, which requires the participation of Glu. This study reveals a previously unrecognized IL-17-Glu-energy metabolism axis, which is important for osteoclast differentiation and contributes to osteoclast-mediated bone loss. Targeting this axis may be a novel therapeutic strategy for osteoporosis and other IL-17-related diseases.