Objective: The aim of the present study was to evaluate the effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) in cosmetic submicron emulsions and submicron emulsion gels on physiological skin parameters during regular application in a clinical set-up. Methods: Formulation morphology was investigated using cryo-transmission electron microscopy. Stability of the employed formulations was determined by photon correlation spectroscopy, measurement of pH and rheological properties. Effect on physiological skin parameters was evaluated during regular application over four weeks in a parallel group study (n = 15, healthy forearm skin) with a Corneometer, Sebumeter, skin-pH-Meter, Aquaflux and an Epsilon sensor. Confocal Raman spectroscopy was employed to monitor urea and NMF levels. Results: Both submicron emulsions and gels showed satisfying storage stability irrespective of cyclodextrin incorporation. No statistically significant effects on skin barrier function and any of the observed parameters were obtained, indicating good skin tolerability of all tested formulations. Conclusion: Results suggest good skin tolerability of the developed cosmetic submicron emulsions and gels with HP-β-CD.