Stress in rodents encompasses a spectrum of physiological, physical, behavioral, immunological, and psychological responses to environmental challenges that disrupt homeostatic equilibrium. While moderate or short-term stress can enhance resilience against external threats, excessive or prolonged stress can lead to significant physiological and psychological dysfunction. It can affect the manifestation and severity of numerous disorders, including diabetes, atherosclerosis, depression, depressive-like behaviors, tumors, and neurochemical toxicity. This article creates findings from different experimental paradigms employed to provoke and assess oxidative and psychological stress, by this means underscoring the synergistic roles of both physiological and psychological stressors in modifying stress responses. Furthermore, it clarifies the underlying mechanisms of stress adaptation, especially the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Also, it recognizes a critical gap in our understanding of stress biology, emphasizing the imperative for further investigation to update the development of targeted therapeutic interventions for stress-related pathologies in both animal and human subjects. In conclusion, chronic restraint stress disrupts energy balance, promotes inflammation and apoptosis, and impairs cellular repair mechanisms in the liver. These findings give insights into the biochemical and molecular pathways underlying stress-induced metabolic and cellular dysfunction, highlighting the importance of stress management in maintaining physiological homeostasis.