Autoimmune disorders, including type 1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE), are influenced by a combination of genetic, environmental, and immunological factors. Among these, stress, both physical and psychological, has been increasingly recognized as a significant contributor to disease onset and progression. This review explores the current literature on the relationship between stress and autoimmune diseases, focusing on the neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal (HPA) axis, and the effects of glucocorticoids on immune modulation. These mechanisms contribute to clinical manifestations, such as disease flares or progression, highlighting the impact of stress on patient outcomes. Evidence suggests that psychological stress can precipitate the onset of T1DM in genetically predisposed individuals, with immune disruptions occurring before diagnosis. In SLE, both acute and chronic stress, particularly trauma-induced stress, has been linked to increased disease activity and flare-ups, largely due to stress-induced immune dysregulation that disrupts the balance between pro-inflammatory and anti-inflammatory cytokines. Despite the substantial evidence supporting the role of stress in autoimmune disease exacerbation, further research is necessary to fully understand the mechanisms by which stress influences autoimmune diseases and to develop effective stress management.