Abstract: Peptide drugs have demonstrated significant potential in the treatment of diabetes, tumors, and immune disorders, however, their oral delivery faces multiple challenges, including gastrointestinal enzymatic degradation, mucus barrier obstruction, and low epithelial permeability, resulting in extremely low bioavailability. Compared to traditional small-molecule drugs, polypeptides exhibit such characteristics as high molecular weight, strong hydrophilicity, and susceptibility to enzymatic degradation, thus their absorption evaluation models require higher physiological relevance and mechanistic specificity. This article reviews various models currently applicable for the evaluation of oral polypeptide preparations, including cell models, ex vivo intestinal sac models, in vivo models, and animal models, with particular focus on analyzing the applicability of these models in the absorption evaluation of peptide drugs, and illustrates their specific applications in oral polypeptide development through case studies, so as to provide a scientific basis for the rational evaluation and model selection for oral polypeptide preparations.