Protein Tyrosine Phosphatase 1B (PTP1B) stands as a pivotal enzyme in cellular signallingpathways, exerting significant influence on metabolism, insulin sensitivity, and cellular proliferation. This review comprehensively explores the pharmacological and chemical dimensions of PTP1B, highlighting its crucial role in regulating cellular processes. The structural elucidation of PTP1B has unveiled key insights into its function and inhibition. Its catalytic domain, featuring a conserved signature motif, serves as a target for pharmacological intervention. Various small molecule inhibitors have been developed to modulate PTP1B activity, with promising implications for treating metabolic disorders such as diabetes and obesity. Additionally, the structural diversity of PTP1B inhibitors offers opportunities for rational drug design and optimization. Beyond their therapeutic relevance, PTP1B inhibitors have emerged as valuable tools for probing cellular signallingnetworks. By selectively perturbing PTP1B function, researchers can dissect the intricate interplay between tyrosine phosphorylation and dephosphorylation events, shedding light on disease mechanisms and identifying novel drug targets. Furthermore, the review explores the diverse applications of PTP1B inhibitors in preclinical and clinical settings, ranging from basic research to drug discovery endeavours. The multifaceted roles of PTP1B inhibitors extend beyond metabolic disorders, encompassing cancer, inflammation, and neurodegenerative diseases. In conclusion, this review underscores the pivotal importance of PTP1B in cellular physiology and disease pathogenesis. By elucidating its pharmacological and chemical aspects, this comprehensive examination provides valuable insights into the development and application of PTP1B-targeted therapies for a myriad of human ailments.