Isoniazid-hydrazone complexes (IHCs) were synthesized and thoroughly characterized by FT-IR, 1H NMR and 13C NMR spectroscopic techniques. The anti-inflammatory and antidiabetic activities were tested for the IHCs using protein denaturation methods and the α-amylase inhibitory method. The molecular modeling studies for IHCs were investigated and their molecular parameters were calculated using Density Functional Theory methods. The IHCs showed lower band gap and higher electrophilicity index values. Further, molecular docking studies were investigated against the α-amylase enzyme to compare the experimental results. The isoniazid hydrazone-salicylic acid complex (3c) showed five hydrogen bonding interactions with amino acid residues of the α-amylase enzyme (1HNY). Display omitted •The synthesis of IHCs is economically cheaper and simple method.•The IHCs proved as anti-inflammatory and antidiabetic agents at in vitro level.•Hydrazone-salicylate complex forms 5 hydrogen bonding interaction with 1HNY.•Electrophilicity index of hydrazone-salicylate complex is higher than others.•FMO studies showed the electron cloud localized in the benzoate and pyridinium.