A series of new extensively conjugated $E$-stilbene azomethines (5a-5h) were synthesized and screened for their antioxidant and antimicrobial activity. The compounds were tested against bacterial (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Bacillus subtilis) and fungal strains (Aspergillus niger, A. flavus, and Trichoderma harzianum) using the agar well diffusion method. Among the tested compounds, $N$'-(4-nitrobenzylidene)-2-(($E)$-styryl)benzohydrazide (5g) was found to possess potent antimicrobial activity higher than some drugs with significant activity reported in the literature, e.g., cefradine and terbinafine hydrochloride. Additionally, compounds 5a-5h were also evaluated for antioxidant potential using DPPH free radical scavenging and ferric thiocyanate (FTC) assays. Among these, $N$'-(4-hydroxybenzylidene)-2-(($E)$-styryl)benzohydrazide (5e) exhibited significant antioxidant potential by both assays. Compound 5e demonstrated higher DPPH free radical scavenging activity (IC$_{50} = 22 \pm 0.19 \mu$ g/m) than the standard, butylated hydroxytoluene (BHT; IC$_{50} =28 \pm 0.10 \mu$ g/mL). A similar trend was observed for compound 5e in FTC assay, which exhibited 86 $\pm$ 0.19% inhibition, whereas the BHT control showed 81 $\pm$ 0.21% inhibition of linoleic acid peroxidase. The structure elucidation of the synthesized compounds was carried out by UV-Vis, FT-IR, $^{1}$H NMR, $^{13}$C NMR, and elemental analysis and mass spectrometry. These results suggest possible use of these compounds for the rational design of new antimicrobial and antioxidant agents.