The synthesis and release of glucocorticoids in living organisms are related to their response to unfavorable stressful conditions in order to maintain homeostatic functions and survive. One such hormone in humans is cortisol, which is produced by the hypothalamic‑pituitary‑adrenal cortex axis and binds with the glucocorticoid receptor (GR) following its secretion. GR controls a number of distinct gene networks. Non‑coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non‑coding RNAs (lncRNAs), regulate the expression and function of GR, having a considerable impact on various biological processes and treatment approaches for numerous disorders. In the present review, the GR pathways and signaling as part of the stress response system are discussed. A detailed report on the role of miRNAs and lncRNAs in glucocorticoid signaling is also presented.