<p>Reactive oxygen species (ROS), inevitable byproducts of aerobic respiration, exhibit both signaling and cytotoxic effects depending on concentration within cells. At controlled levels, ROS serve as crucial signaling molecules mediating intracellular signal transduction pathways. However, excessive accumulation triggers oxidative stress, leading to oxidative damage that disrupts protein structure and function, ultimately inducing cell death. Enhancing cellular adaptive responses to oxidative stress and mitigating intracellular ROS accumulation are therefore critical strategies for maintaining cellular homeostasis. This approach significantly improves product yield and underpins its widespread application across diverse sectors, including functional foods, pharmaceuticals, and cosmeceuticals. This review first delineates the origins and multifaceted roles of ROS. Subsequently, it details strategies employed to bolster cellular oxidative stress resilience, focusing on process optimization and metabolic engineering approaches. Finally, synthesizing current research advances, existing challenges, and emerging trends, the review outlines future research directions aimed at enhancing the oxidative stress tolerance of microbial cell factories.</p> Graphical abstract <p></p>