G-protein-coupled receptors (GPCRs) play a crucial role in the gene regulation of processes related to the response to different types of stress in fungi. These receptors act as sensors of extracellular signals and transmit the information to the interior of the cell through G-proteins. In the presence of different and specific types of stresses, GPCRs activate signaling cascades that culminate in the activation of transcription factors, which regulate the expression of genes associated with the stress response, including those induced by changes in environmental pH. GPCR-mediated gene regulation allows fungi to adapt to adverse conditions such as osmotic, thermal, oxidative, or nutritional stress, as well as fluctuations in environmental pH. This review focuses on the understanding of how GPCRs modulate the stress response in fungi and their crucial role in advancing our knowledge of the physiology and adaptability of these microorganisms in their changing environment.