Equol has been shown to improve skin health and regeneration, due to its antioxidative, phytoestrogenic and epigenetic characteristics. The effects of a topical intervention on skin structure, telomere length and epigenetic markers in skin cells were analysed. Sixty-four participants were divided in four groups and three of them treated topically with the following: emulsion with Equol powder (Isoflavandiol-E-55-RS®); emulsion with microencapsulated Equol (Vesisorb® Isoflavandiol-E-55-RS®) and an emulsion with lecithin (Vesisorb® placebo). A control group of 6 volunteers did not receive any intervention. The active compound was a 0.5% equol-racemate. For 58 participants, all samples were collected. Structural analysis, molecular analysis and questionnaires were performed at the start of the study and after 8 weeks of intervention, twice a day. Structural skin parameters were analysed by Visioscan® VC 98 and Cutometer® dual MPA 580. Molecular analyses from epidermal cells collected by skin stripping of the forehead included telomere length and LINE-1 methylation, following DNA extraction, bisulfite conversion and qPCR as well as high-resolution melting curve analysis. Effects of nutrition and lifestyle habits were evaluated with a standardized food and lifestyle questionnaire. The surface analysis showed significant improvements in skin roughness, skin texture and skin smoothness after both interventions. Cutometer® dual MPA 580 measurement revealed improvement of skin firmness and elasticity parameters for both preparations. A decrease in mean LINE-1 methylation (n.s.) and telomere length (sign. P < 0.05) was observed in the sample group with age. In the treated groups, significantly longer telomeres were observed after intervention. Whether changes in telomere length reflect changes in the regulation of telomerase, epigenetic interactions or turnover of keratinocytes needs further research. Stability and availability of preparations in skin seems to be high as not many significant differences in the activity of pure or encapsulated substances were seen. The results of this study indicate that equol has beneficial effects on structural as well as molecular skin parameters and encourages further investigations to decipher the epigenetic regulation of skin ageing and interactions of equol.