<p>Incontinence-associated dermatitis (IAD) is a common complication resulting from prolonged exposure to moisture, irritants, and microbial load, leading to skin barrier breakdown and infection risk. Although incontinence wipes support routine hygiene, their effectiveness varies due to differences in substrate properties, antimicrobial activity, and user acceptability. This study developed and evaluated wipes formulated with chlorhexidine gluconate (CHG; 3–5%), benzalkonium chloride (BKC; 0.1–0.2%), and silver nitrate (SN; 0.005–0.01%) using two substrates: 100% viscose and a 50/50 polyester–viscose (P/V) blend. Physical characterization showed similar porosity between fabrics, with the P/V blend demonstrating superior structural stability and fluid retention under pressure, while viscose exhibited higher water holding capacity. Antimicrobial testing using zone-of-inhibition assays identified CHG 5% as the most effective formulation against both Gram-positive and Gram-negative uropathogens; BKC and SN showed limited activity against Gram-negative strains. Pressure-induced liquid release and cyclic loading tests further confirmed that the P/V blend provided better mechanical resilience during wet use. Sensory evaluation with 10 volunteers yielded comparable ratings for comfort, cleanliness, dryness, residue, and temperature sensation, with odor as the primary differentiating factor. SN formulations received the highest odor preference, followed by CHG 5% and BKC 0.2%. Kendall’s coefficient of concordance showed significant agreement only for odor ratings. Overall, CHG 5% offered the strongest antimicrobial efficacy, the P/V blend delivered enhanced durability, and SN wipes achieved the highest user acceptability. These results underscore the need for further formulation optimization and real-world validation to develop effective, user-centered wipes for IAD prevention.</p> Graphical Abstract <p></p>