The inhibition of dipeptidyl peptidase IV (DPP-IV, E.C.3.4.14.5) is well recognized as a new avenue for the treatment of Type 2 diabetes (T2D). Until now, peptide-like DDP-IV inhibitors have been shown to normalize the blood glucose concentration in T2D subjects. To the best of our knowledge, there is yet no computational model for predicting and analyzing DPP-IV inhibitory peptides using sequence information. In this study, we present for the first time a simple and easily interpretable sequence-based predictor using the scoring card method (SCM) for modeling the bioactivity of DPP-IV inhibitory peptides (iDPPIV-SCM). Particularly, the iDPPIV-SCM was developed by employing the SCM method together with the propensity scores of amino acids. Rigorous independent test results demonstrated that the proposed iDPPIV-SCM was found to be superior to those of well-known machine learning (ML) classifiers (e.g. k-nearest neighbor, logistic regression and decision tree) with demonstrated improvements of 2-11%, 4-22% and 7-10% for accuracy, MCC and AUC, respectively, while also achieving comparable results to that of support vector machine. Furthermore, the analysis of estimated propensity scores of amino acids as derived from the iDPPIV-SCM was performed so as to provide a more in-depth understanding on the molecular basis for enhancing the DPP-IV inhibitory potency. Taken together, these results revealed that iDPPIV-SCM was superior to those of other well-known ML classifiers owing to its simplicity, interpretability and validity. For the convenience of biologists, the predictive model is deployed as a publicly accessible web server at http://camt.pythonanywhere.com/iDPPIV-SCM. It is anticipated that iDPPIV-SCM can serve as an important tool for the rapid screening of promising DPP-IV inhibitory peptides prior to their synthesis.