This study evaluates the relative beneficial effects of 10% dietary intake of fructooligosaccharides (FOSs) and isomaltooligosaccharides (IMOs) and combination of FOS + IMO in poloxamer-407 (PX-407) induced type 2 diabetic Wistar rats. FOSs was produced from Aspergillus oryzae (MTCC5154) while IMOs and standards of 1-kestose, 1-nystose, 1-fructofuranosyl nystose and panose were procured. In silico docking studies were performed by GLIDE program for each of the FOSs and IMOs for PPAR-gamma activation and DPP-IV inhibition. Diabetic rats treated with FOS + IMO showed relatively more amelioration of glycemic and lipid dysmetabolism, remarkable reduction in oxidative markers, increased GLP-1 content as well as Bifidobacterial Lactobacilli population in caecum than lone FOSs/IMOs treatment. Out of nine oligosaccharides docked from FOS and IMO; panose, nystose and kestose showed highest ranking binding mode with DPP-IV and PPAR-y and were selected for in vitro study either alone or in combinations. On its own nystose showed potent DPP-1V inhibitory activity with an IC50 of 146.8 mu M while panose at 20.2 mu M concentrations showed 50% binding ability to PPAR-gamma-LBD. Combinations of oligosaccharides tested namely Nys + Pan, Nys + Kes and Pan + Kes demonstrated significant (p <0.001) effect on PPAR-gamma/DPP-IV bioassay. The results provide pharmacological evidence of FOSs and IMOs as antihyperglycemic mediated by their interaction with multiple targets operating in diabetes particularly nystose and pannose. (C) 2014 Elsevier Ltd. All rights reserved.