This review explores the role of hypoxia-inducible factor (HIF-1) and oxidative stress in tendon degeneration, highlighting their molecular mechanisms and potential therapeutic strategies. Tendons, composed mainly of collagen, are susceptible to mechanical stress and can develop tendinopathy due to chronic overuse, leading to microtrauma and degeneration. Hypoxia, a physiological condition in tendons, promotes HIF-1 expression, which regulates angiogenesis, inflammation, and cell survival, potentially exacerbating tendon degeneration. Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, also contributes to tendon damage by promoting apoptosis and ECM degradation. Antioxidants such as Vitamin C, Curcumin, Nicotinamide Mononucleotide (NMN), and Superoxide Dismutase (SOD) have been shown to promote tendon repair. HIF-1α is degraded under normoxia but accumulates under hypoxia, leading to increased VEGF expression and neo-angiogenesis, which can impair tendon healing. HIF-1α overexpression in tendinopathy is associated with structural alterations, increased apoptosis, and inflammation. Modulating HIF-1α levels may be a therapeutic strategy for tendinopathy. Hypoxia also promotes the proliferation and differentiation of tendon-derived stem cells (TDSCs), which can aid in tendon repair. However, prolonged hypoxia can lead to excessive scarring and ECM degradation. Oxidative stress, mediated by NOX enzymes, contributes to tendon damage, and antioxidants like DHEA, quercetin, and NMN have shown promise in reducing oxidative stress and promoting tendon healing. Antioxidant therapy may be a viable treatment for tendon disorders. The regulation of HIF-1 and oxidative stress pathways could provide new therapeutic targets for tendon repair.This review explores the role of hypoxia-inducible factor (HIF-1) and oxidative stress in tendon degeneration, highlighting their molecular mechanisms and potential therapeutic strategies. Tendons, composed mainly of collagen, are susceptible to mechanical stress and can develop tendinopathy due to chronic overuse, leading to microtrauma and degeneration. Hypoxia, a physiological condition in tendons, promotes HIF-1 expression, which regulates angiogenesis, inflammation, and cell survival, potentially exacerbating tendon degeneration. Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, also contributes to tendon damage by promoting apoptosis and ECM degradation. Antioxidants such as Vitamin C, Curcumin, Nicotinamide Mononucleotide (NMN), and Superoxide Dismutase (SOD) have been shown to promote tendon repair. HIF-1α is degraded under normoxia but accumulates under hypoxia, leading to increased VEGF expression and neo-angiogenesis, which can impair tendon healing. HIF-1α overexpression in tendinopathy is associated with structural alterations, increased apoptosis, and inflammation. Modulating HIF-1α levels may be a therapeutic strategy for tendinopathy. Hypoxia also promotes the proliferation and differentiation of tendon-derived stem cells (TDSCs), which can aid in tendon repair. However, prolonged hypoxia can lead to excessive scarring and ECM degradation. Oxidative stress, mediated by NOX enzymes, contributes to tendon damage, and antioxidants like DHEA, quercetin, and NMN have shown promise in reducing oxidative stress and promoting tendon healing. Antioxidant therapy may be a viable treatment for tendon disorders. The regulation of HIF-1 and oxidative stress pathways could provide new therapeutic targets for tendon repair.