Reactive oxygen species (ROS) play a critical role in cellular signaling and homeostasis, influencing various physiological and pathological processes. This review summarizes the mechanisms by which ROS interact with key signaling pathways, including NF-κB, MAPKs, Keap1-Nrf2-ARE, PI3K-Akt, Ca²⁺, and the mPTP. ROS are generated through mitochondrial respiration and NADPH oxidases, and their levels are regulated by antioxidant enzymes such as SOD, GPx, and GST-pi. ROS can modulate the activity of signaling proteins, ion channels, and transporters, affecting cellular functions such as proliferation, apoptosis, and inflammation. ROS influence the NF-κB pathway by modulating the phosphorylation and ubiquitination of IκBα, thereby controlling NF-κB activation. Similarly, ROS regulate MAPK pathways by affecting the activation of ERK, JNK, and p38, which are involved in cell survival, differentiation, and stress responses. The Keap1-Nrf2-ARE pathway is crucial for maintaining redox balance and protecting against oxidative stress, with ROS inducing the dissociation of Keap1 from Nrf2, leading to the activation of Nrf2 and the expression of antioxidant genes. ROS also interact with Ca²⁺ signaling, influencing the release and uptake of Ca²⁺, which in turn affects ROS production and cellular functions. The mPTP, a key mitochondrial channel, is regulated by ROS, leading to mitochondrial dysfunction and apoptosis. Additionally, ROS modulate protein kinases such as PKA, PKC, and CaMKII by oxidizing cysteine residues, thereby affecting signaling pathways and cellular responses. The ubiquitination/proteasome system is also influenced by ROS, with oxidative stress affecting the activity of E1, E2, and E3 enzymes, leading to the degradation of key proteins such as Nrf2 and IKKβ. Overall, ROS play a central role in regulating cellular signaling and homeostasis, and understanding their interactions with signaling pathways is essential for developing therapeutic strategies to combat diseases associated with oxidative stress.Reactive oxygen species (ROS) play a critical role in cellular signaling and homeostasis, influencing various physiological and pathological processes. This review summarizes the mechanisms by which ROS interact with key signaling pathways, including NF-κB, MAPKs, Keap1-Nrf2-ARE, PI3K-Akt, Ca²⁺, and the mPTP. ROS are generated through mitochondrial respiration and NADPH oxidases, and their levels are regulated by antioxidant enzymes such as SOD, GPx, and GST-pi. ROS can modulate the activity of signaling proteins, ion channels, and transporters, affecting cellular functions such as proliferation, apoptosis, and inflammation. ROS influence the NF-κB pathway by modulating the phosphorylation and ubiquitination of IκBα, thereby controlling NF-κB activation. Similarly, ROS regulate MAPK pathways by affecting the activation of ERK, JNK, and p38, which are involved in cell survival, differentiation, and stress responses. The Keap1-Nrf2-ARE pathway is crucial for maintaining redox balance and protecting against oxidative stress, with ROS inducing the dissociation of Keap1 from Nrf2, leading to the activation of Nrf2 and the expression of antioxidant genes. ROS also interact with Ca²⁺ signaling, influencing the release and uptake of Ca²⁺, which in turn affects ROS production and cellular functions. The mPTP, a key mitochondrial channel, is regulated by ROS, leading to mitochondrial dysfunction and apoptosis. Additionally, ROS modulate protein kinases such as PKA, PKC, and CaMKII by oxidizing cysteine residues, thereby affecting signaling pathways and cellular responses. The ubiquitination/proteasome system is also influenced by ROS, with oxidative stress affecting the activity of E1, E2, and E3 enzymes, leading to the degradation of key proteins such as Nrf2 and IKKβ. Overall, ROS play a central role in regulating cellular signaling and homeostasis, and understanding their interactions with signaling pathways is essential for developing therapeutic strategies to combat diseases associated with oxidative stress.