A study of the interaction between cell membranes and small molecules derived from lignin, a protective phenolic biopolymer found in vascular plants, is crucial for identifying their potential as pharmacological and toxicological agents. In this work, the interactions of model cell membranes [supported 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers] are compared for three βO4 dimers of coniferyl alcohol (G lignin monomer): guaiacylglycerol guaiacol ester with a hydroxypropenyl (HOC3H4-) tail (G-βO4′-G), a truncated GG dimer without HOC3H4- (G-βO4′-truncG), and a benzylated GG dimer (benzG-βO4′-G). The uptake of the lignin dimers (per mass of lipid) and the energy dissipation (a measure of bilayer disorder) are higher for benzG-βO4′-G and G-βO4′-truncG than those for G-βO4′-G in the gel-phase DPPC bilayer, as measured using quartz crystal microbalance with dissipation (QCM-D). A similar uptake of G-βO4′-truncG is observed for a fluid-phase bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine, suggesting that the effect of the bilayer phase on dimer uptake is minimal. The effects of increasing lignin dimer concentration are examined through an analysis of density profiles, potential of mean force curves, lipid order parameters, and bilayer area compressibilities (disorder) in the lipid bilayers obtained from molecular dynamics simulations. Dimer distributions and potentials of mean force indicate that the penetration into bilayers is higher for benzG-βO4′-G and G-βO4′-truncG than that for G-βO4′-G, consistent with the QCM-D results. Increased lipid tail disorder due to dimer penetration leads to a thinning and softening of the bilayers. Minor differences in the structure of lignin derivatives (such as truncating the hydroxypropenyl tail) have significant impacts on their ability to penetrate lipid bilayers.