Introduction: G-protein Coupled Receptors (GPCRs) are the largest family of classical membrane receptors and the most important class of pharmacological targets, playing roles in many physiological and pathological processes. Targeting a GPCR is a challenging approach because traditional drugs and similar therapeutics have a number of significant drawbacks, including low aqueous solubility, low bioavailability, rapid metabolic degradation, low tissue specificity, and off-target effects. This review discusses different nanocarrier-based drug delivery strategies to improve the therapeutic efficacy, targeting efficiency, and translational potential of drugs acting on GPCRs. Methods: A systematic review of peer-reviewed published articles to explore the latest developments in GPCR biology, GPCR signalling pathways, and drug delivery using nanocarriers was conducted. Major nanoplatforms, such as liposomes, polymeric nanoparticles, dendrimers, and hybrid nanosystems, were studied based on their design principles, targeting strategies, and therapeutic applications. Preclinical, mechanistic, and early translational studies that were relevant were included. Results: Nanocarrier-based systems have multiple advantages in GPCR-targeted therapy, such as enhanced drug stability, increased bioavailability, controlled release, and reduced systemic toxicity. Functionalization of nanocarriers may improve delivery in a receptor-specific manner and facilitate transport across biological barriers, such as the blood-brain barrier. These systems also support multiple functions, including co-delivery of therapeutics, nucleic acids, and diagnostic components. Promising applications have been identified in oncology, neurological disorders, cardiovascular diseases, and inflammatory conditions. However, there are still challenges in translation, particularly with regard to immunogenicity, long-term safety, manufacturing scalability, and regulatory approval. Discussion: The combined use of GPCR pharmacology with state-of-the-art nanocarrier engineering is a promising approach to improve receptor selectivity and therapeutic precision. Novel instruments, such as artificial intelligence, molecular modelling, and systems pharmacology, may further aid the optimisation of ligand selection, carrier design, and personalised therapeutic development. Conclusion: Nanocarrier-mediated drug delivery is a sensible and highly promising strategy to address the limitations of conventional GPCR therapeutics. In addition, developments in targeted nanomedicine may accelerate the development of accurate and individualised GPCR-targeted therapeutic treatments. DOI:10.2174/0113894501460624260723074236