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Poly(ADP-ribose) polymerase (PARP) inhibitors constitute the inaugural targeted therapy shown to enhance the prognosis of individuals with hereditary tumors, initially utilized in the management of patients with germline BRCA1/2-associated breast cancer. With ongoing research, PARP inhibitors (PARPi) are currently under extensive investigation for their applicability across a spectrum of diseases, encompassing oncology, cardiovascular diseases, and cerebrovascular diseases. This narrative review provides a comprehensive synthesis of the biological rationale, existing evidence, recent advancements, and prospective future directions of PARPi in the treatment of cancers, cardiovascular diseases, and cerebrovascular disorders. We provide a comprehensive overview of the recent advancements, advantages, and limitations associated with both clinically approved and investigational PARPi. Beyond their application in oncology, PARPi demonstrate significant potential in other therapeutic domains, including cardiovascular diseases. As our comprehension of the biological functions of PARP and its molecular mechanisms advances, it is anticipated that the therapeutic applications of these inhibitors will broaden considerably. Future research endeavors should prioritize the identification of predictive biomarkers across various diseases and the development of strategies to circumvent drug resistance. Consequently, the integration of fundamental and clinical research on PARPi across diverse diseases is essential to establish a foundational framework for clinical translation.