P2Y receptors (P2YRs), a δ group of rhodopsin-like G protein-coupled receptors (GPCRs), have many essential functions in physiology and pathology, such as platelet aggregation, immune responses, neuroprotective effects, inflammation, and cellular proliferation; thus, they are among the most researched therapeutic targets for use in the clinical treatment of diseases (e.g., clopidogrel, an antithrombotic drug, and Prolacria, a treatment for dry eye). Over the past two decades, GPCRs have been revealed to transmit signals as dimers to increase the diversity of signalling pathways or pharmacological activities. Many studies have frequently confirmed dimerization between P2YRs and other GPCRs due to their functions in cardiovascular and cerebrovascular processes in vivo and in vitro. Recently, some P2YR dimers that dynamically balance physiological functions in the body were shown to be involved in effective signal transduction and exert pathological pharmacological effects. In this review, we summarize the types, pharmacological changes, and active regulators of P2YR-related dimerization. In summary, our review delineates that P2YR-related dimers have new functions and pharmacological activities and maybe a novel direction to improve the effectiveness of medications such as thrombotic events associated with COVID-19.