Since recombinant biotherapeutics were accepted in the therapeutic drug market, one of the significant challenges has been the insufficient circulatory half-life of many protein and peptide-based drugs. To overcome this pharmacokinetic limitation, serum albumin has been widely utilized as a molecular carrier due to its intrinsic FcRn-mediated recycling mechanism. Besides human drugs, there is also a significant need for extended half-lives of pet or veterinary drug therapeutics, making the development of albumin-binding domains with cross-species reactivity necessary. VNARs represent the antigen-binding domains of Immunoglobulin new antigen receptors (IgNARs) found in cartilaginous fish (e.g. sharks), which exhibit unique structural properties and hold significant potential for clinical diagnosis and treatment. In this study, we constructed a phage display library by immunizing the white-spotted bamboo shark with human serum albumin (HSA). Through multiple rounds of panning using both human and mouse serum albumins, VNAR-4A12 was successfully screened. Affinity tests verified that VNAR-4A12 exhibited cross-reactivity to multiple serum albumin homologues. Additionally, the structural basis for this cross-reactivity was confirmed, and it was demonstrated that 4A12-sfGFP exhibited prolonged exposure compared to sfGFP in vivo. This multispecies targeting strategy addresses critical limitations in both human and veterinary pharmaceutical development, offering new opportunities for long-term therapy.