Over-expression of alpha-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed alpha-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro alpha-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including H-1, C-13 NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising alpha-amylase inhibitory activities (IC50 = 1.23 +/- 0.06-4.5 +/- 0.03 pM) as compared to the standard acarbose (IC50 1.20 +/- 0.09 mu M). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 +/- 0.13-5.3 +/- 0.11) and ABTS (IC50 = 2.34 +/- 0.07-5.5 +/- 0.07 mu M) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 +/- 0.09 mu M, and IC50 2.03 +/- 0.11 mu M for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of alpha-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.