The incorporation of drugs and bioactive compounds in the natural rubber latex (NRL) matrix has been an alternative for the development of transdermal release membranes. Ibuprofen (IBF) is known to be used to treat inflammatory diseases, but when administered orally, high concentrations can cause some adverse problems. In this work, the incorporation of IBF in the NRL membranes was evaluated by physical-chemical, in vitro permeation, hemocompatibility and molecular modeling assays. In addition, the in vitro release profile of IBF in acid and basic media was analyzed during 96 h. The IBF-NRL membrane exhibited the absence of intermolecular bonding that could hinder drug release and presented compatible mechanical properties for applications as a cutaneous adhesive (0.58 and 1.12 MPa to Young’s modulus and rupture tension, respectively). The IBF-NRL system did not present a significant hemolysis degree (1.67%) within 24 h. The release test indicated that in the first hours of the study, 48.5% IBF was released at basic pH and 22.5% at acidic pH, which is characteristic of a burst effect. Then, a stable release profile was observed until the end of the assay, with total IBF release of 60% in alkaline medium and 50% in acidic medium. The drug permeation results indicated that the IBF-NRL membranes can be used for the local skin treatment with permeation of 3.11% of IBF. Dynamic Molecular simulations indicated a pronounced electric dipole in the ionized form of IBF, which suggests a more effective interaction with water, explaining the efficient drug release in alkaline solutions. In general, the results demonstrate that the IBF-NRL membrane has great potential for a new adhesive that can be used for the treatment of inflammatory processes and injuries.