Interleukin-10 (IL-10) as an anti-inflammatory cytokine has been reported as a protective factor against dry skin in type 2 diabetes mellitus (T2DM). Centella asiatica (CA) could increase IL-10 thus improve dry skin in diabetes mellitus. This study aims to evaluate the effects of CA on stratum corneum (SC) IL-10 levels of T2DM patients. A total of 154 subjects with T2DM were included from metabolic and endocrine outpatient clinic at Dr. Cipto Mangunkusumo Hospital and 5 primary healthcare facilities in Jakarta, Indonesia. Subjects were randomized into three groups receiving combination of oral CA (2 × 1100 mg) and topical 1% CA ointment (CAo + CAt group); oral placebo and topical CA (Plo + CAt group); or oral placebo and topical placebo (Plo + Plt group). All interventions were given twice daily for 28 days. Skin samples were obtained through skin stripping on day 0 and 29. Subgroup analysis was conducted based on HbA1c and random blood glucose levels. An increase of IL-10 was found in CAo + CAt group of well-controlled and partially-controlled blood glucose subgroups, not statistically significant. There were significant improvements of SRRC (Specified Symptom Sum Score) and SCap (Skin Capacitance) in well-controlled blood glucose CAo + CAt group compared to Plo + Plt group on day 29. A combination of oral and topical CA showed increase in IL-10 levels in SC, as well as improvement in SRRC and SCap. Combination treatment of oral and topical CA is beneficial for the treatment of dry skin in T2DM patients. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.