Diabetes mellitus is one of the fastest-growing metabolic disorders. Worldwide, one out of 10 people suffer from diabetes mellitus. In this manuscript, we establish the antidiabetic potential of previously synthesized pyridazine derivatives using in silico and in vitro experiments. Molecular docking studies of pyridazine derivatives with pullulanase Amy12, isomaltase, and alpha-amylase receptors revealed that Molecules 45, 46, and 29 showed good docking interaction scores. ADMET analysis of the top three docked pyridazine derivatives (45, 46, and 29) showed lesser solubility and poor distribution behavior. Molecules 45, 46, and 29 maintained drug-like properties with good oral bioavailability. Molecules 45 and 29 showed reproductive toxicity without any sign of mutagenicity, tumorigenicity, or other irritancy. Molecule 46 emerged as a nontoxic molecule in all aspects. In vitro alpha-amylase inhibition data of molecules 45, 46, 29, and acarbose showed IC50 values of 8.67, 8.46, 8.83, and 66.65 μg/mL, respectively. The antidiabetic activity of pyridazine derivatives is increased with the presence of phenothiazine coupled with a biphenyl group, indole with a biphenyl group, and phenothiazine with an ethylphenyl group. Establishing these pyridazine derivatives using in vivo experiments could be beneficial in managing diabetes.