The kisspeptin system controls hormones that affect fertility, metabolism, and even cancer growth. Scientists are hunting for drugs that can turn this system on (agonists) or off (antagonists), using lab tests and AI tools, but most of these compounds are still experimental and not available for personal use.

The kisspeptin/kisspeptin receptor (<i>KISS1</i>/<i>KISS1R</i>) system has emerged as a vital regulator of various physiological processes, including cancer progression, metabolic function, and reproduction. <i>KISS1R</i>, a member of the G protein-coupled receptor family, is crucial for regulating the hypothalamic/pituitary/gonadal axis. A growing number of <i>KISS1R</i> agonists are currently being investigated in clinical trials, whereas the number of antagonists remains limited. Most existing ligands are synthetic peptides, with only a few small-molecule compounds, such as musk ambrette, having been identified. In this article, we provide an overview of the <i>KISS1</i>/<i>KISS1R</i> system and its involvement in diseases such as reproductive disorders, cancer, diabetes, and cardiovascular disease. We also highlight the various technologies used to identify <i>KISS1R</i> ligands, including radioligand binding assays, calcium flux assays, IP1 formation assays, ERK phosphorylation assays, qRT-PCR, and AI-based virtual screening. Furthermore, we discuss the latest advances in identifying <i>KISS1R</i> agonists and antagonists, highlighting ongoing challenges and future directions in research. These insights lay the groundwork for future research aimed at leveraging this system for developing innovative therapeutic strategies across a range of medical conditions.