INTRODUCTION: The incorporation of 4D printing alongside chemical stimuli-responsive hydrogels represents a significant advancement in the field of biomedical engineering, effectively overcoming the constraints associated with conventional static 3D-printed structures. Through the integration of time as the fourth dimension, 4D printing facilitates the development of dynamic and adaptable structures that can react to chemical alterations in their surroundings. This innovation presents considerable promise for sophisticated tissue engineering and targeted drug delivery applications. AREAS COVERED: This review examines the function of chemical stimuli-responsive hydrogels within the context of 4D printing, highlighting their distinctive ability to undergo regulated transformations when exposed to particular chemical stimuli. An in-depth examination of contemporary research underscores the collaborative dynamics between these hydrogels and their surroundings, focusing specifically on their utilization in biomimetic scaffolds for tissue regeneration and the advancement of intelligent drug delivery systems. EXPERT OPINION: The integration of 4D printing technology with chemically responsive hydrogels presents exceptional prospects for advancements in tissue engineering and targeted drug delivery, facilitating the development of personalized and adaptive medical solutions. Although the potential is promising, it is essential to address challenges such as material optimization, biocompatibility, and precise control over stimuli-responsive behavior to facilitate clinical translation and scalability.