Surfactants present in cleansing formulations interact not only with the unwanted lipids accumulating on the human skin (dirt) but also with its protective lipidic layer (sebum). Development of simple models of human sebum would help to compare different surfactants and biosurfactants under the same conditions. In this contribution we propose a first monolayer model of synthetic sebum composed of lard, stearic acid, lanolin, squalane and cholesterol. The monolayer compression isotherm features a gas-liquid (G-LE1), two liquid-liquid transitions (LE1-LE2 and LE2-LC), and a collapse at πcoll = 45 mN/m. The monolayer spread on pure water and pre-compressed to π0 = 30 mN/m was exposed to four synthetic surfactants (sodium lauryl sulfate (SLS), sodium laureth sulfate (SLES), ammonium lauryl sulfate (ALS) and cocamidopropyl betaine (CAPB)) and four plant extracts (oat (Avena sativa L.), horse chestnut (Aesculus hippocastanum L.), cowherb (Vaccaria hispanica [P. Mill.] Rauschert), soybean (Glycine max L.) and soapwort (Saponaria officinalis L.)) introduced to the subphase at a dry mass content of 1% (w/w). Three modes of the monolayer-(bio)surfactant interactions were observed: (1) complete solubilization (SLS, SLES, ALS, CAPB); (2) penetration accompanied by an increase of surface pressure and elasticity but without solubilization (horse chestnut, cowherb, soapwort); (3) no interaction (oat, soybean).