Introduction Intensified hand hygiene measures were recommended for preventing the spread of SARS‐CoV‐2. However, these measures can lead to skin damage and the development of hand eczema, particularly among health professionals. Objectives This pilot study aimed to evaluate the effects of repeated antiseptic use on healthy skin under controlled conditions and to assess the emollient use. Methods Twelve healthy volunteers (nine females, age = 22.3 ± 2.8 years (mean ± SD), Fitzpatrick phototypes II and III) with no skin diseases were recruited. Antiseptic was applied daily for 3 weeks on the volar sides of forearms. Emollient cream was also applied daily. Skin assessments were performed using non‐invasive methods (transepidermal water loss—TEWL, skin hydration, erythema and melanin content). Results Prolonged antiseptic use increased TEWL, decreased hydration and elevated erythema and melanin levels. Emollient cream significantly reduced TEWL and improved hydration on antiseptic‐treated sites, and also enhanced hydration on intact skin. Conclusions Prolonged use of antiseptics can have adverse effects on the skin, including barrier disruption and inflammation. Emollient showed promise in improving skin hydration and reducing the damage caused by antiseptics. Further research with a larger sample is needed to confirm these findings and assess emollient efficacy during frequent antiseptic use. This pilot study established a controlled model to assess the impact of prolonged chlorhexidine‐based antiseptic use on skin. Healthy participants underwent a three‐week regimen, revealing that prolonged antiseptic use damaged the skin barrier, with elevated transepidermal water loss and reduced hydration. Topical emollient treatment mitigated damage, suggesting potential protective effects.