In the present study, fruit seeds such as Mangifera indica (mango), Phoenix dactylifera (dates), Annona reticulata (custard apple), Citrullus lanatus (water melon), Artocarpus heterophyllus (jack fruit) and Prunus domestica (plum) were screened for the pancreatic α-amylase inhibitory activity. The HWEs of Prunus domestica and Phoenix dactylifera seeds possess highest (98.09 ± 1.3%) and lowest (51.20 ± 3.8%) inhibitory activities, respectively. RSM mediated studies of Phoenix dactylifera showed a significant improvement (99.24 ± 0.5%) in the amylase inhibitory activity at an optimal condition of 70°C, 150 rpm, 7.5 minutes and 1:15 material ratio. The HPLC/DAD/MS analysis of PTLC eluate of Prunus domestica has revealed the presence of polyphenols such as quercetin, flavonoid glycoside melonate, genistein, chalcone derivative, 3,8’-diprenyl,5,7,4’-trihydroxy flavonone and isosakurametin. Similar analysis recorded for Phoenix dactylifera has showed the presence of O- hexosyltricin and 3,4 - dicaffeoylquinic acid. The studies concluded the significant pancreatic α-amylase inhibitory effect of Prunus domestica and Phoenix dactylifera seeds.