Hydrogels are three-dimensional polymeric systems, being able to accommodate different categories of bioactive agents and act as promising drug delivery systems in many different biomedical applications. Due to their extended 3D network, hydrogels exhibit many advantages, such as extensive loading capacity and controlled drug release profiles, combined with characteristics such as biocompatibility and biodegradability, due to their constructive polymeric biomaterials. Moreover, hydrogels are capable of being administered via different routes of administration, including systemic and topical ones, due to their tunable characteristics. Stimuli-responsive hydrogels are characterized as smart biomaterials, while environmental stimuli, such as pH, can be employed to trigger on-demand drug release from the hydrogels via the provocation of conformational changes. In the present study, an emphasis on the pH-responsive hydrogels is taking place through various literature cases in drug delivery, wound healing, and some alternative applications, including implantation, oral administration, etc., wherein many different polymeric derivatives have been utilized. Moreover, the role of each used polymer or polymeric combination with other functional biomaterials, their mode of structure formation (for example, crosslinking), and their content release mechanism are highlighted, as well as the therapeutic effect of the hydrogels on different pathological conditions, as promising candidates for pharmaceutical applications.