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This research work succinctly covers the significance and vital role of gliptins in diabetes management and in the potential areas of further antidiabetic research, making it a strong drug candidate for antidiabetic drug development. We illustrated herein molecular docking, synthesis, and biological evaluation of selected potent synthesized molecules. Additionally, all the potent compounds were characterized by means of MASS and NMR spectral analysis, whereas the purity of these molecules were assessed by HPLC method. In order to determine the efficacy and cytotoxicity of synthesized gliptin\u2010based scaffolds, <jats:italic>in\u2010vitro<\/jats:italic> anti\u2010oxidant and MTT assays with the implantation of DPPH and THP\u20101\u2005cell lines, respectively, were performed. The results data disclose the anti\u2010oxidant and biosafety potential of the newly schemed compounds. Based on <jats:italic>in\u2010vitro<\/jats:italic> screening outcomes, only a derivative that exhibited potent efficacy was selected and subjected to an <jats:italic>in\u2010vivo<\/jats:italic> study. Among them, compounds <jats:bold>6<\/jats:bold> and <jats:bold>12<\/jats:bold> are the most potent ones, which exhibited % radical scavenge of <jats:bold>89<\/jats:bold>.38\u2009% and <jats:bold>91<\/jats:bold>.58\u2009% related to standard ascorbic acid <jats:bold>(91<\/jats:bold>.58\u2009%<jats:bold>)<\/jats:bold>. Surprisingly, these compounds also exhibited excellent anti\u2010diabetic efficacy at a dose of 4\u2005mg\/kg in an <jats:italic>in\u2010vivo<\/jats:italic> animal model. In conclusion, all studies suggested that the titled molecules could be promising lead compounds for the treatment of patients with type 2 diabetes mellitus.<\/jats:p>","DOI":"10.1002\/cbdv.202401890","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T16:59:27Z","timestamp":1732899567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and Evaluation of Antidiabetic Potential of Gliptin\u2010based Hybrid Scaffolds"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-0851","authenticated-orcid":false,"given":"Shaikh","family":"Yahya","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry School of Pharmaceutical Education and Research  Jamia Hamdard 110062 New Delhi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0722-4835","authenticated-orcid":false,"given":"Vivek Kumar","family":"Gour","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry School of Pharmaceutical Education and Research  Jamia Hamdard 110062 New Delhi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaiprakash","family":"Sangshetti","sequence":"additional","affiliation":[{"name":"Y. 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