Background Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging‐associated epidermal dysfunction has been connected to elevations in circulating cytokines. Objective We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment. Methods This randomized, open‐label pilot trial was carried out in two cities in northern China. A total of 200 participants aged ≥65 years were randomly assigned to the emollient‐treated and untreated groups at 1:1 ratio. Participants in the treated group were treated topically with Atopalm cream® twice‐daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of cognitive impairment, while epidermal biophysical properties were measured on the forearms and the shins in parallel. Results Over the three‐year trial, GDS significantly increased from baseline (P < 0.0001) in the controls, while in the treated group, GDS stabilized. While stratum corneum hydration on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls (P < 0.0001). On the forearms of the treated group, stratum corneum hydration increased (P < 0.0001) while skin surface pH decreased from baseline (P < 0.0001). Conclusions These results suggest that improvements in epidermal function with topical emollient can mitigate the progression of cognitive impairment. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results.