Curcumin (CCM) is a molecule of particular interest in health applications due to its wide spectrum of benefits for humans. However, its water-insoluble character and low bioavailability have so far prevented its extended use as a therapeutic agent. Incorporation of CCM in drug delivery vehicles (liposomes, vesicles, exosomes, etc.) is expected to contribute to increasing its bioavailability. Studies of the affinity of CCM with the components of the membrane systems of such vehicles and determination of factors that may enhance curcumin entrapment in biological membranes are of fundamental importance. To that end, here we take advantage of the nanoarchitectonic capabilities of the Langmuir technique for the construction of model cell membranes and determination of thermodynamic properties in mixed films. The obtained results may serve to: (i) provide some light on the miscibility of CCM with the components in the cell membrane and (ii) determine the optimal conditions for the fabrication of membrane systems incorporating CCM. For that, binary and ternary mixed Langmuir films of CCM, DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and CHOL (cholesterol) have been prepared. Whilst binary mixtures of DPPC and CCM exhibit poor miscibility and even phase segregation, CHOL has shown itself as a key element to promote the incorporation of CCM in the phospholipidic membrane containing DPPC. Both the thermodynamic studies of the ternary Langmuir films and the Atomic Force Microscopy (AFM) images of Langmuir–Blodgett films have shown that ternary mixed films with a molar fraction composition of x_DPPC/x_CHOL/x_CCM = 0.4/0.4/0.2 exhibit good miscibility, stability, and result in monolayers with a very homogeneous topography.