A better understanding of skin lipidomics and its alteration under treatment administration might offer therapeutic solutions for seborrhea. To quantitatively and qualitatively explore the lipid-modifying effect of the moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid (LDCS) in seborrhea participants with and without acne vulgaris (AV). We conducted an open-label explorative study on 20 seborrhea participants (10 AV and 10 non-AV). All participants applied LDCS for 8 weeks with the addition of benzoyl peroxide 2.5% gel and adapalene 0.1%/benzoyl peroxide 2.5% gel in AV. Skin surface lipid (SSL) assessments were performed biweekly, using Sebumeter® and lipid-absorbent Sebutapes® to collect forehead SSL for profile analysis by gas chromatography-mass spectrometry (GC-MS). SSL amount significantly decreased since week 2 in AV (p-value=0.0124) and week 6 in non-AV (p-value=0.0098), respectively. Twenty-two important SSLs were annotated from GC-MS analysis, comprising 19 free fatty acids, cholesterol, squalene, and glycerol. There was a significant reduction in 5 and 13 lipid components in AV and non-AV groups, respectively. LDCS, either alone or with topical acne treatment, demonstrated substantial sebusuppressive and lipid-modifying effects among seborrhea participants.