DBP, a representative PAR leucine zipper transcriptional activator intricately involved in circadian rhythm regulation, has garnered considerable attention for its potential therapeutic role in ameliorating metabolic disorders and modulating pharmacokinetic processes. In this review, we systematically elucidate the mechanisms underlying DBP’s involvement within the circadian rhythm regulatory network and its subsequent influence on pharmacokinetics. DBP, functioning as a D-box binding protein, is transcriptionally regulated by the CLOCK/BMAL1 signaling pathway and interacts synergistically with ROR/REV-ERB-mediated transcriptional regulation of NFIL3, ultimately controlling the expression of core circadian genes, such as PER. Furthermore, DBP significantly affect drug absorption and metabolism in peripheral tissues by modulating various drug-metabolizing enzymes, transporter proteins, and hormonal pathways. These findings underscore the potential of DBP as a key regulator of circadian rhythm disorders and a pivotal factor in optimizing drug bioavailability. The comprehensive summary presented herein highlights DBP’s clinical significance in addressing circadian-related pathologies, managing associated chronic diseases, and improving pharmacotherapeutic efficacy. Additionally, this review provides novel insights and therapeutic targets that could inform future advancements in drug delivery systems and pharmacological research.