<p>The global increase in antimicrobial resistance, along with the role of pathological angiogenesis in infection-associated inflammation, underscores the need for multifunctional therapeutic agents. In this study, a series of riparin-type benzamides were synthesized using efficient and accessible synthetic methods, yielding structurally diverse compounds, and their antimicrobial and antiangiogenic potential was evaluated. Among these, riparin III (<b>3c</b>) exhibited the most potent and broad-spectrum antimicrobial activity, effectively inhibiting Gram-positive and Gram-negative bacterial strains as well as <i>Candida</i> spp. Furthermore, riparin I (<b>3a</b>), riparin II (<b>3b</b>), and riparin III (<b>3c</b>) exhibited antiangiogenic activity, suggesting their potential therapeutic relevance in infection-associated inflammation. Toxicity assessments indicated low cytotoxicity at the effective concentrations, supporting the safety profile of the compounds. Molecular docking analysis corroborated the in vitro findings, revealing strong interactions between riparin I (<b>3a</b>) and fungal cell wall targets, as well as between riparin III (<b>3c</b>) and key bacterial enzymes involved in resistance and replication. Overall, these results highlight riparin I (<b>3a</b>), riparin II (<b>3b</b>), and riparin III (<b>3c</b>) as promising multifunctional candidates for the development of antimicrobial agents capable of addressing the current challenges in infection control, including antimicrobial resistance and inflammation-associated&#xa0;pathologies.</p> Graphical Abstract <p></p>