Herein, a library of novel pyridone derivatives 1-34 was designed, synthesized, and evaluated for alpha-amylase and alpha-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1-34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1-34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC50 = 14.87 +/- 0.16 mu M) but compounds 13 and 12 were found to be the most potent compounds with IC50 values of 9.20 +/- 0.14 mu M and 3.05 +/- 0.18 mu M against alpha-amylase and alpha-glucosidase enzymes, respectively. Compounds 1-34 also displayed moderate antioxidant potential in the range of IC50 = 96.50 +/- 0.45 to 189.98 +/- 1.00 mu M in comparison to the control butylated hydroxytoluene (BHT) (IC50 = 66.50 +/- 0.36 mu M), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1-34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.