Chalcones, open-chain flavonoids with an α, β-unsaturated carbonyl system, are widely recognized for diverse biological activities, including antimicrobial and antioxidant effects. In the present study, ten chalcone derivatives (C1–C10) were synthesized using Claisen–Schmidt condensation and characterized by melting point, yield, and recrystallization profiles. Their antimicrobial activity was evaluated against Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli using the broth microdilution method, while antioxidant potential was determined by the DPPH radical scavenging assay. The antimicrobial results indicated that chalcones bearing electron-withdrawing substituents (–Cl, –Br, –CN, –NO₂) exhibited enhanced antibacterial effects. In contrast, derivatives with electron-donating groups (–OH, –OCH₃) displayed stronger antioxidant activity, as, C1, which demonstrated low IC₅₀ values compared with the standard ascorbic acid. These findings establish a clear structure–activity relationship (SAR), suggesting that chalcones with electron-withdrawing groups are promising antibacterial agents, whereas those with electron-donating groups serve as potent antioxidants. Overall, the synthesized chalcone derivatives highlight the potential of structural modification in improving therapeutic efficacy and may serve as lead scaffolds for the development of novel antimicrobial and antioxidant agents.